Journal articles: 'Α/γ Peptide'

1

Amorín, M., V. Villaverde, L. Castedo, and J. R. Granja. "New α,γ-peptide tubulets." Journal of Drug Delivery Science and Technology 15, no. 1 (2005): 87–92. http://dx.doi.org/10.1016/s1773-2247(05)50011-x.

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Bandyopadhyay, Anupam, and Hosahudya N. Gopi. "Hybrid Peptides: Direct Transformation of α/α, β-Unsaturated γ-Hybrid Peptides to α/γ-Hybrid Peptide 12-Helices." Organic Letters 14, no. 11 (May 18, 2012): 2770–73. http://dx.doi.org/10.1021/ol300987d.

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Roussel-Jazédé, Virginie, Jesús Arenas, Jeroen D. Langereis, Jan Tommassen, and Peter van Ulsen. "Variable processing of the IgA protease autotransporter at the cell surface of Neisseria meningitidis." Microbiology 160, no. 11 (November 1, 2014): 2421–31. http://dx.doi.org/10.1099/mic.0.082511-0.

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As with all classical monomeric autotransporters, IgA protease of Neisseria meningitidis is a modular protein consisting of an N-terminal signal sequence, a passenger domain and a C-terminal translocator domain (TD) that assists in the secretion of the passenger domain across the outer membrane. The passenger of IgA protease consists of three separate domains: the protease domain, the γ-peptide and the α-peptide that contains nuclear localization signals (NLSs). The protease domain is released into the extracellular milieu either via autocatalytic processing or via cleavage by another autotransporter, NalP, expression of which is phase-variable. NalP-mediated cleavage results in the release of a passenger that includes the α- and γ-peptides. Here, we studied the fate of the α-peptide when NalP was not expressed and observed strain-dependent differences. In meningococcal strains where the α-peptide contained a single NLS, the α-peptide remained covalently attached to the TD and was detected at the cell surface. In other strains, the α-peptide contained four NLSs and was separated from the TD by an IgA protease autoproteolytic cleavage site. In many of those cases, the α-peptide was found non-covalently associated with the cells as a separate polypeptide. The cell surface association of the α-peptides may be relevant physiologically. We report a novel function for the α-peptide, i.e. the binding of heparin – an immune-modulatory molecule that in the host is found in the extracellular matrix and connected to cell surfaces.

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Legrand, Baptiste, and Ludovic T. Maillard. "α,β‐Unsaturated γ‐Peptide Foldamers." ChemPlusChem 86, no. 4 (April 2021): 629–45. http://dx.doi.org/10.1002/cplu.202100045.

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Misra, Rajkumar, Gijo George, Abhijith Saseendran, Srinivasarao Raghothama, and Hosahudya N. Gopi. "Ambidextrous α,γ‐Hybrid Peptide Foldamers." Chemistry – An Asian Journal 14, no. 23 (November 28, 2019): 4408–14. http://dx.doi.org/10.1002/asia.201901411.

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Amorín, Manuel, Roberto J. Brea, Luis Castedo, and Juan R. Granja. "The Smallest α,γ-Peptide Nanotubulet Segments: Cyclic α,γ-Tetrapeptide Dimers." Organic Letters 7, no. 21 (October 2005): 4681–84. http://dx.doi.org/10.1021/ol0518885.

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7

Hirao, Takashi, Masahide Sato, Akira Shirahata, and Yoshiyuki Kamio. "Covalent Linkage of Polyamines to Peptidoglycan inAnaerovibrio lipolytica." Journal of Bacteriology 182, no. 4 (February 15, 2000): 1154–57. http://dx.doi.org/10.1128/jb.182.4.1154-1157.2000.

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ABSTRACT Spermidine and cadaverine were found to be constituents of the cell wall peptidoglycan of Anaerovibrio lipolytica, a strictly anaerobic bacterium. The peptidoglycan was degraded with theN-acetylmuramyl-l-alanine amidase and endopeptidase into two peptide fragments, peptide I and peptide II, at a molar ratio of 4:1. Peptides I and II were identified asl-alanine–d-glutamic acid(αcadaverine)γ meso-diaminopimelic acid (DAP)–d-alanine andl-alanine–d-glutamic acid(αspermidine)γ meso-DAP–d-alanine, respectively. The N1-amino group of spermidine was linked to the α-carboxyl group of the d-glutamic acid residue of peptide II.

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Mustafa, Ghulam, Hafiza Salaha Mahrosh, Mahwish Salman, Sumaira Sharif, Raheela Jabeen, Tanveer Majeed, and Hafsah Tahir. "Identification of Peptides as Novel Inhibitors to Target IFN-γ, IL-3, and TNF-α in Systemic Lupus Erythematosus." BioMed Research International 2021 (November 13, 2021): 1–11. http://dx.doi.org/10.1155/2021/1124055.

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Autoimmune disorder is a chronic immune imbalance which is developed through a series of pathways. The defect in B cells, T cells, and lack of self-tolerance has been greatly associated with the onset of many types of autoimmune complications including rheumatoid arthritis, systemic lupus erythematosus (SLE), multiple sclerosis, and chronic inflammatory demyelinating polyneuropathy. The SLE is an autoimmune disease with a common type of lupus that causes tissue and organ damage due to the wide spread of inflammation. In the current study, twenty anti-inflammatory peptides derived from plant and animal sources were docked as ligands or peptides counter to proinflammatory cytokines. Interferon gamma (IFN-γ), interleukin 3 (IL-3), and tumor necrosis factor alpha (TNF-α) were targeted in this study as these are involved in the pathogenesis of SLE in many clinical studies. Two docking approaches (i.e., protein-ligand docking and peptide-protein docking) were employed in this study using Molecular Operating Environment (MOE) software and HADDOCK web server, respectively. Amongst docked twenty peptides, the peptide DEDTQAMMPFR with S -score of -11.3018 and HADDOCK score of − 10.3 ± 2.5 kcal/mol showed the best binding interactions and energy validation with active amino acids of IFN-γ protein in both docking approaches. Depending upon these results, this peptide could be used as a potential drug candidate to target IFN-γ, IL-3, and TNF-α proteins to control inflammatory events. Other peptides (i.e., QEPQESQQ and FRDEHKK) also revealed good binding affinity with IFN-γ with S -scores of -10.98 and -10.55, respectively. Similarly, the peptides KHDRGDEF, FRDEHKK, and QEPQESQQ showed best binding interactions with IL-3 with S -scores of -8.81, -8.64, and -8.17, respectively.

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Dutta, Arpita, Suven Das, Purak Das, Suvendu Maity, Prasanta Ghosh, and Soumya Shankha Biswas. "Unique supramolecular assembly of a synthetic achiral α, γ-hybrid tripeptide." Zeitschrift für Kristallographie - Crystalline Materials 237, no. 1-3 (March 1, 2022): 77–81. http://dx.doi.org/10.1515/zkri-2022-0002.

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Abstract An achiral tripeptide, namely, Boc-γ-Abu-m-ABA-Aib-OMe (γ-Abu: γ−amino butyric acid; m-ABA: meta-aminobenzoic acid) was synthesized by solution phase procedure. The α, γ-hybrid peptide was designed in such a way that two dissimilar γ−amino acids, one flexible and another rigid, were positioned sidewise along with α-amino isobutyric acid (Aib) as C-terminal residue. The single crystal X-ray diffraction analysis revealed that two kinks were generated around centrally placed m-ABA. Interestingly, the peptide self-assembled via three intermolecular N–H···O and one intermolecular C–H···O hydrogen bonding interactions to supramlecular helical architecture.

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Passero, Christopher J., Marcelo D. Carattino, Ossama B. Kashlan, Mike M. Myerburg, Rebecca P. Hughey, and Thomas R. Kleyman. "Defining an inhibitory domain in the gamma subunit of the epithelial sodium channel." American Journal of Physiology-Renal Physiology 299, no. 4 (October 2010): F854—F861. http://dx.doi.org/10.1152/ajprenal.00316.2010.

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Proteases activate the epithelial sodium channel (ENaC) by cleaving the large extracellular domains of the α- and γ-subunits and releasing peptides with inhibitory properties. Furin and prostasin activate mouse ENaC by cleaving the γ-subunit at sites flanking a 43 residue inhibitory tract (γE144-K186). To determine whether there is a minimal inhibitory region within this 43 residue tract, we generated serial deletions in the inhibitory tract of the γ-subunit in channels resistant to cleavage by furin and prostasin. We found that partial or complete deletion of a short segment in the γ-subunit, R158-N171, enhanced channel activity. Synthetic peptides overlapping this segment in the γ-subunit further identified a key 11-mer tract, R158-F168 (RFLNLIPLLVF), which inhibited wild-type ENaC expressed in Xenopus laevis oocytes, and endogenous channels in mpkCCD cells and human airway epithelia. Further studies with amino acid-substituted peptides defined residues that are required for inhibition in this key 11-mer tract. The presence of the native γ inhibitory tract in ENaC weakened the intrinsic binding constant of the 11-mer peptide inhibitor, suggesting that the γ inhibitory tract and the 11-mer peptide interact at overlapping sites within the channel.

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11

Fenger, M., and A. H. Johnsen. "α-Amidated peptides derived from pro-opiomelanocortin in human pituitary tumours." Journal of Endocrinology 118, no. 2 (August 1988): 329–38. http://dx.doi.org/10.1677/joe.0.1180329.

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ABSTRACT Human pituitary tumours, obtained at surgery for Cushing's disease and Nelson's syndrome, were extracted and the content and molecular forms of proopiomelanocortin (POMC)-derived peptides determined by radioimmunoassay, gel chromatography, reversed-phase high-performance liquid chromatography (HPLC) and sequence analysis. In the tumours from patients with Cushing's disease the mean concentrations of amidated peptides relative to the total amount of POMC were as follows: α-MSH, 1·7%; amidated γ-MSH (γ1-MSH), 8·5% and the peptide linking γ-MSH and ACTH in the precursor (hinge peptide or joining peptide) in its amidated form (HP-N), 17·1%. The same relative concentrations in the tumours from patients with Nelson's syndrome were 8·5% (α-MSH), 7·5% (γ1-MSH) and 12·2% (HP-N). More than 95% of the ACTH(1–39) immunoreactivity eluted as synthetic ACTH(1–39) by gel chromatography and HPLC. The remaining ACTH(1–39) immunoreactivity eluted as partly glycosylated high molecular weight forms. All the α-MSH and its glycine-extended precursor ACTH(1–14) were of low molecular weight, mainly non- or mono-acetylated forms, but significant amounts of diacetylated analogues were also present. γ1-MSH and γ2-MSH immunoreactivities eluted as high molecular weight forms and were partly glycosylated. No low molecular weight forms of γ1-MSH or γ2-MSH could be detected in the pituitary tumours. Amidated hinge peptide was mainly of the 30 amino acid form. In conclusion, all the molecular forms of the amidated peptides detected in tumours from patients with Cushing's disease and Nelson's syndrome were similar to the molecular forms found in the normal human pituitary. The main difference between the tumours and the normal pituitary was the greater amount of peptides produced, particularly α-MSH and γ1-MSH. J. Endocr. (1988) 118, 329–338

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Misra, Rajkumar, Rahi M. Reja, Lagumaddepalli V. Narendra, Gijo George, Srinivasarao Raghothama, and Hosahudya N. Gopi. "Exploring structural features of folded peptide architectures in the construction of nanomaterials." Chemical Communications 52, no. 61 (2016): 9597–600. http://dx.doi.org/10.1039/c6cc04502b.

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13

Breloer, Minka, Bernhard Fleischer, and Arne von Bonin. "In Vivo and In Vitro Activation of T Cells After Administration of Ag-Negative Heat Shock Proteins." Journal of Immunology 162, no. 6 (March 15, 1999): 3141–47. http://dx.doi.org/10.4049/jimmunol.162.6.3141.

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Abstract Heat shock proteins (HSP) Hsp70 and gp96 prime class I-restricted cytotoxic T cells against Ags present in the cells from which they were isolated. The immunization capacity of HSPs is believed to rely on their ability to bind antigenic peptides. In this study, we employed the well-established OVA and β-galactosidase (β-gal) antigenic model systems. We show that in vitro long-term established OVA and β-gal-specific CTL clones release TNF-α and IFN-γ when incubated with Ag-negative Hsp70 and gp96. In the absence of antigenic peptides, HSP-mediated secretion of TNF-α and IFN-γ requires cell contact of the APC with the T cell but is not MHC-I restricted. Moreover, Hsp70 molecules purified from Ag-negative tissue, e.g., negative for antigenic peptide, are able to activate T cells in vivo, leading to significant higher frequencies in OVA-specific CD8+ T cells. In unprimed animals, these T cells lyse OVA-transfected cell lines and produce TNF-α and IFN-γ after Ag stimulus. Taken together our data show that, besides the well-established HSP/peptide-specific CTL induction and activation, a second mechanism exists by which Hsp70 and gp96 molecules activate T cells in vivo and in vitro.

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14

Tung, Y. C. Loraine, Sarah J. Piper, Debra Yeung, Stephen O’Rahilly, and Anthony P. Coll. "A Comparative Study of the Central Effects of Specific Proopiomelancortin (POMC)-Derived Melanocortin Peptides on Food Intake and Body Weight in Pomc Null Mice." Endocrinology 147, no. 12 (December 1, 2006): 5940–47. http://dx.doi.org/10.1210/en.2006-0866.

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Functional disruption of either MC3R or MC4R results in obesity, implicating both in the control of energy homeostasis. The ligands for these receptors are derived from the prohormone proopiomelancortin (POMC), which is posttranslationally processed to produce a set of melanocortin peptides with a range of activities at the MC3R and MC4R. The relative importance of each of these peptides α-MSH, γ3-MSH, γ2-MSH, γ-lipotropin (γ-LPH) and, in man but not in rodents, β-MSH] in the maintenance of energy homeostasis is, as yet, unclear. To investigate this further, equimolar amounts (2 nmol) of each peptide were centrally administered to freely feeding, corticosterone-supplemented, Pomc null (Pomc−/−) mice. After a single dose at the onset of the dark cycle, α-MSH had the most potent anorexigenic effect, reducing food intake to 35% of sham-treated animals. β-MSH, γ-LPH, and γ3- and γ2-MSH all reduced food intake but to a lesser degree. The effects of peptide administration over 3 d were also assessed. Only α-MSH significantly reduced body weight, affecting both fat and lean mass. Other peptides had no significant effect on body weight. Pair-feeding of sham-treated mice to those treated with α-MSH resulted in identical changes in total weight, fat and lean mass indicating that the effects of α-MSH were primarily due to reduced food intake rather than increased energy expenditure. Although other melanocortins can reduce food intake in the short-term, only α-MSH can reduce the excess fat and lean mass found in Pomc−/− mice, mediated largely through an effect on food intake.

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Kairane, Ceslava, Riina Mahlapuu, Kersti Ehrlich, Kalle Kilk, Mihkel Zilmer, and Ursel Soomets. "Diverse Effects of Glutathione and UPF Peptides on Antioxidant Defense System in Human Erythroleukemia Cells K562." International Journal of Peptides 2012 (February 15, 2012): 1–5. http://dx.doi.org/10.1155/2012/124163.

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The main goal of the present paper was to examine the influence of the replacement of γ-Glu moiety to α-Glu in glutathione and in its antioxidative tetrapeptidic analogue UPF1 (Tyr(Me)-γ-Glu-Cys-Gly), resulting in α-GSH and UPF17 (Tyr(Me)-Glu-Cys-Gly), on the antioxidative defense system in K562 cells. UPF1 and GSH increased while UPF17 and α-GSH decreased the activity of CuZnSOD in K562 cells, at peptide concentration of 10 μM by 42% and 38% or 35% and 24%, respectively. After three-hour incubation, UPF1 increased and UPF17 decreased the intracellular level of total GSH. Additionally, it was shown that UPF1 is not degraded by γ-glutamyltranspeptidase, which performs glutathione breakdown. These results indicate that effective antioxidative character of peptides does not depend only on the reactivity of the thiol group, but also of the other functional groups, and on the spatial structure of peptides.

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Tamm, Lukas K., and Xing Han. "Viral Fusion Peptides: A Tool Set to Disrupt and Connect Biological Membranes." Bioscience Reports 20, no. 6 (December 1, 2000): 501–18. http://dx.doi.org/10.1023/a:1010406920417.

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The structure and function of viral fusion peptides are reviewed. The fusion peptides of influenza virus hemagglutinin and human immunodeficiency virus are used as paradigms. Fusion peptides associated with lipid bilayers are conformationally polymorphic. Current evidence suggests that the fusion-promoting state is the obliquely inserted α-helix. Fusion peptides also have a tendency to self-associate into γ-sheets at membrane surfaces. Although the conformational conversion between α- and γ-states is reversible under controlled conditions, its physiological relevance is not yet known. The energetics of peptide insertion and self-association could be measured recently using more soluble “second generation” fusion peptides. Fusion peptides have been reported to change membrane curvature and the state of hydration of membrane surfaces. The combined results are built into a model for the mechanism by which fusion peptides are proposed to assist in biological membrane fusion.

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Chatterjee, Sunanda, Rituparna Sinha Roy, and P. Balaram. "Expanding the polypeptide backbone: hydrogen-bonded conformations in hybrid polypeptides containing the higher homologues of α-amino acids." Journal of The Royal Society Interface 4, no. 15 (January 23, 2007): 587–606. http://dx.doi.org/10.1098/rsif.2006.0203.

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Half a century has passed since the hydrogen-bonded secondary structures of polypeptides and proteins were first recognized. An extraordinary wealth of conformational information is now available on peptides and proteins, which are formed of α-amino acid residues. More recently, the discovery of well-folded structures in oligopeptides containing β-amino acids has focused a great deal of current interest on the conformational properties of peptides constructed from higher homologues (ω) of α-amino acids. This review examines the nature of intramolecularly hydrogen-bonded conformations of hybrid peptides formed by amino acid residues, with a varying number of backbone atoms. The β-turn, a ubiquitous structural feature formed by two residue (αα) segments in proteins and peptides, is stabilized by a 10-atom (C 10 ) intramolecular 4→1 hydrogen bond. Hybrid turns may be classified by comparison with their αα counterparts. The available crystallographic information on hydrogen-bonded hybrid turns is surveyed in this review. Several recent examples demonstrate that individual ω-amino acid residues and hybrid dipeptide segments may be incorporated into the regular structures of α-peptides. Examples of both peptide helices and hairpins are presented. The present review explores the relationships between folded conformations in hybrid sequences and their counterparts in all α-residue sequences. The use of stereochemically constrained ω-residues promises to expand the range of peptide design strategies to include ω-amino acids. This approach is exemplified by well-folded structures like the C 12 (αγ) and C 14 (γγ) helices formed in short peptides containing multiply substituted γ-residues. The achiral γ-residue gabapentin is a readily accessible building block in the design of peptides containing γ-amino acids. The construction of globular polypeptide structures using diverse hybrid sequences appears to be a realistic possibility.

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18

Diós, Ádám, Rita Elek, Ildikó Szabó, Szilvia Horváth, Judit Gyimesi, Róbert Király, Katharina Werkstetter, Sibylle Koletzko, László Fésüs, and Ilma R. Korponay-Szabó. "Gamma-gliadin specific celiac disease antibodies recognize p31-43 and p57-68 alpha gliadin peptides in deamidation related manner as a result of cross-reaction." Amino Acids 53, no. 7 (May 31, 2021): 1051–63. http://dx.doi.org/10.1007/s00726-021-03006-7.

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AbstractCeliac disease (CeD) is a T-cell-dependent enteropathy with autoimmune features where tissue transglutaminase (TG2)-mediated posttranslational modification of gliadin peptides has a decisive role in the pathomechanism. The humoral immune response is reported to target mainly TG2-deamidated γ-gliadin peptides. However, α-gliadin peptides, like p57-68, playing a crucial role in the T-cell response, and p31-43, a major trigger of innate responses, also contain B-cell gliadin epitopes and γ-gliadin like motifs. We aimed to identify if there are anti-gliadin-specific antibodies in CeD patients targeting the p31-43 and p57-68 peptides and to examine whether deamidation of these peptides could increase their antigenicity. We explored TG2-mediated deamidation of the p31-43 and p57-68 peptides, and investigated serum antibody reactivity toward the native and deamidated α and γ-gliadin peptides in children with confirmed CeD and in prospectively followed infants at increased risk for developing CeD. We affinity-purified antibody populations utilizing different single peptide gliadin antigens and tested their binding preferences for cross-reactivity in real-time interaction assays based on bio-layer interferometry. Our results demonstrate that there is serum reactivity toward p31-43 and p57-68 peptides, which is due to cross-reactive γ-gliadin specific antibodies. These γ-gliadin specific antibodies represent the first appearing antibody population in infancy and they dominate the serum reactivity of CeD patients even later on and without preference for deamidation. However, for the homologous epitope sequences in α-gliadins shorter than the core QPEQPFP heptapeptide, deamidation facilitates antibody recognition. These findings reveal the presence of cross-reactive antibodies in CeD patients recognizing the disease-relevant α-gliadins.

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Reiriz, César, Manuel Amorín, Rebeca García-Fandiño, Luis Castedo, and Juan R. Granja. "α,γ-Cyclic peptide ensembles with a hydroxylated cavity." Organic & Biomolecular Chemistry 7, no. 21 (2009): 4358. http://dx.doi.org/10.1039/b911247m.

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20

Cunnick, J., C. Twamley, I. Udovichenko, K. Gonzalez, and D. J. Takemoto. "Identification of a binding site on retinal transducin α for the phosphodiesterase inhibitory γ subunit." Biochemical Journal 297, no. 1 (January 1, 1994): 87–91. http://dx.doi.org/10.1042/bj2970087.

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Transducin alpha (T alpha) activates retinal rod cyclic GMP phosphodiesterase (PDE) by interacting with and removing the inhibitory PDE gamma subunit. A T alpha-PDE gamma complex can be isolated in vitro, and our previous work [Morrison, Rider and Takemoto (1987) FEBS Lett. 222, 266-270; Morrison, Cunnick, Oppert and Takemoto (1989) J. Biol. Chem. 264, 11671-11681] has identified a region of PDE gamma, residues 24-45, that binds to T alpha. The C-terminal region of PDE gamma is the site that interacts with PDE alpha/beta and inhibits catalytic function. The site on T alpha that binds to the PDE gamma 24-45 region has not been identified. Synthetic peptides (15-mers) which span the bovine T alpha sequence were tested for binding to purified recombinant PDE gamma using a solid-phase assay. The peptides were also tested for ability to activate a PDE complex. We have identified a region, residues 250-275 of T alpha, which shows a high affinity of PDE gamma and for the PDE gamma (24-45) binding peptide. The peptide did not bind to the C-terminal residues 50-87 of PDE gamma. Likewise, a region of T alpha, 1-25 did not exhibit high-affinity binding to PDE gamma or to the 24-45 PDE gamma peptide. Specific binding of the 250-275 peptide to PDE gamma was confirmed by its ability to compete with T alpha binding to PDE gamma, although a higher concentration was required (10x). The T alpha-(250-275) peptide activated a fully inhibited PDE alpha beta gamma 2 complex in a dose-dependent manner. These results suggest that a region on T alpha that recognizes the PDE gamma-binding site is found within residues 250-275 of T alpha.

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Mohri, Hiroshi, and Takao Ohkubo. "Effects of Hybrid Peptide Analogs to Receptor Recognition Domains on α- and γ-Chains of Human Fibrinogen on Fibrinogen Binding to Platelets." Thrombosis and Haemostasis 69, no. 05 (1993): 490–95. http://dx.doi.org/10.1055/s-0038-1651639.

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SummaryWe synthesized a series of hybrid peptides that correspond to the γ-chain dodecapeptide (400-411), variable numbers of glycine residues, and the RGDS peptide [Y-HHLGGAK-QAGDV(G) n RGDS] to investigate the relationship of these receptor recognition domains of fibrinogen to platelet membrane glycoprotein IIb/IIIa. The tetrapeptide RGDS, the GRGDSPA peptide and the dodecapeptide inhibited binding of fibrinogen to GPIIb/IIIa by 50% (IC50) at concentrations of 17 ± 1.6 μM, 15 ± 2.1 μM, and 87 ± 6.8 μM, respectively. The inhibitory effect of hybrid peptides increased as the number of glycine residues increased, plateauing with 9-11 glycine residues in hybrid peptide analogs, which had an IC50 of 0.68 ± 0.14 μM. These hybrid peptides completely inhibited the binding of fibrinogen to activated platelets when used in sufficient concentrations. The peptide Y-HHLGGAKQAGDV(G)9RGDS blocked ADP-induced aggregation in citrated platelet-rich plasma with IC50 of 3.5 ± 0.6 μM. When the peptide Y-HHLGGAK-QAGDV(G)9RGDS was labeled with 125I to quantify its binding to platelets, maximal binding was observed within 30 min. The binding sites of the hybrid peptide were 43,600 molecules/platelet (K d = 3.1 ± 0.5 × 10-7 M) to stimulated platelets and 12,500 molecules/platelet (K d = 1.4 ± 0.2 × 10-7 M) to nonstimulated platelets. The hybrid peptides had the same binding affinity to platelets as fibrinogen and inhibited platelet function. Moreover, anti-GPIIb/IIIa antibody inhibited the binding of the labeled hybrid peptide to stimulated platelets. These results indicate that in the native fibrinogen molecule the presence of both RGD sequence or γ-chain domain at optimal distances increased the binding affinity to GPIIb/IIIa. These domains may be the source of hybrid peptide, expanding a new class of platelet inhibitors that act at membrane receptors for adhesive proteins.

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Adibzadeh Sereshgi, Mohammad Mehdi, Sahar Salimi, and Hassan Noorbazargan. "AK2 Antibacterial Synthetic Peptide Can Potentiate Macrophage Responses." ImmunoRegulation 4, no. 2 (January 1, 2022): 73–82. http://dx.doi.org/10.32598/immunoregulation.4.2.1.

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Background: Emphasis on substitutional medications with the elevated bacterial resistance to current antibiotics is pivotal. We evaluated the antibacterial effect of AK2 by Minimum Bactericidal Concentration (MBC) and Minimum inhibitory Concentration (MIC) and its impact on macrophage responses in 17 strains of pathogenic bacteria. The gene expression of macrophage’s cytokines was evaluated. Accordingly, the bioinformatic assessment predicted this peptide’s physicochemical characteristics, behavior, and structures. The present study aimed to assess the antibacterial effect of AK2 peptides on Macrophage responses. Materials and Methods: Cytotoxicity level was assessed by MTT assay on the HeLa cell line. The hemolytic activity of peptides on red blood cells was evaluated. The Griess assay was performed to assess the amount of macrophage nitric oxide production. The real-time PCR method measured the iNOS, IFN-γ, and TNF-α gene expression in isolated macrophages. Results: Peptide concentrations (13-60 µg/mL) were observed as the MBC and MIC value results for various bacteria. No remarkable cytotoxicity was observed at 30 and 60 µg/ml concentrations after 24h. iNOS, IFN-γ, and TNF-α gene expression were upregulated. There was also a higher secretion of nitric oxide in 48 hour-culture of the cell line with peptide. Great antibacterial activity was observed in some bacterial strains, particularly B. melitensis. Conclusion: AK2 peptides display suitable antibacterial activity with negligible toxicity for host cells. This peptide could also stimulate macrophage responses through nitric oxide production and gene expression in proinflammatory cytokines.

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Rezaei Araghi, Raheleh, Carsten C. Mahrenholz, Rudolf Volkmer, and Beate Koksch. "Investigation of the network of preferred interactions in an artificial coiled-coil association using the peptide array technique." Beilstein Journal of Organic Chemistry 8 (April 25, 2012): 640–49. http://dx.doi.org/10.3762/bjoc.8.71.

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We screened a randomized library and identified natural peptides that bound selectively to a chimeric peptide containing α-, β- and γ-amino acids. The SPOT arrays provide a means for the systematic study of the possible interaction space accessible to the αβγ-chimera. The mutational analysis reveals the dependence of the binding affinities of α-peptides to the αβγ-chimera, on the hydrophobicity and bulkiness of the side chains at the corresponding hydrophobic interface. The stability of the resulting heteroassemblies was further confirmed in solution by CD and thermal denaturation.

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Lowry, Philip. "60 YEARS OF POMC: Purification and biological characterisation of melanotrophins and corticotrophins." Journal of Molecular Endocrinology 56, no. 4 (May 2016): T1—T12. http://dx.doi.org/10.1530/jme-15-0260.

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The remarkable conservation of the primary structures and anatomical location of dogfish α-melanocyte-stimulating hormone (MSH), corticotrophin-like intermediate lobe peptide (CLIP) and adrenocorticotrophic hormone (ACTH) compared with mammals reinforced the tissue-specific processing hypothesis of ACTH peptides in the pituitary gland. The cloning of dogfish pro-opiomelanocortin (POMC) led to the identification of δ-MSH and simultaneously revealed the high conservation of the γ-MSH sequence during evolution. These studies have also shown that β-MSH is much less conserved during evolution and in some species is not even processed from β-LPH. Human pro-γ-MSH potentiates the corticosteroidogenic activity of ACTH and peptides generated from its N-terminal, in particular big-γ-MSH, appear to have adrenal mitogenic activity. Human big-γ-MSH (from the zona intermedia) may also cause the adrenache. The review finishes with a cautionary note with regard to the misdiagnosis of the ectopic ACTH syndrome in which partial processing of ACTH can result in large concentrations of α-MSH and CLIP, which can interfere in the performance of two-site immunoassays, and the problem of the correct disulphide bridge arrangement in synthetic N-POMC peptides is also discussed.

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Haldar, Ujjal, Abhishek Pan, Ishita Mukherjee, and Priyadarsi De. "POSS semitelechelic Aβ17–19 peptide initiated helical polypeptides and their structural diversity in aqueous medium." Polymer Chemistry 7, no. 40 (2016): 6231–40. http://dx.doi.org/10.1039/c6py01399f.

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Polyhedral oligomeric silsesquioxane (POSS) semitelechelic Aβ_17–19 peptide which initiated polymerization of γ-benzyl l-glutamate N-carboxyanhydride (BLG-NCA) was studied to prepare peptide–polypeptide conjugates with α-helical conformation.

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HAVERKAMP, SILKE, HELGA KOLB, TODD A. BLUTE, LUXIANG CAO, and WILLIAM D. ELDRED. "Gamma-atrial natriuretic peptide 1–25 is found in bipolar cells in turtle and rat retinas." Visual Neuroscience 16, no. 4 (July 1999): 771–79. http://dx.doi.org/10.1017/s0952523899164150.

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Immunocytochemistry was used to reveal a population of bipolar cells that contain γ-atrial natriuretic peptide 1–25 (γ-ANP) in turtle retina. This same antibody was also used in rat retina as a comparative control. The retinas were examined by both conventional light microscopy and confocal microscopy with double-labeling to determine whether protein kinase C-α-like immunoreactivity (PKC-α-LI) was colocalized with the γ-ANP-LI. Some thick sections of turtle retina immunostained with only the γ-ANP antibody were also examined by electron microscopy. In rat, a subpopulation of bipolar cells with axons terminating close to the ganglion cell layer was labeled. Double-labeling experiments indicated that the γ-ANP-LI and PKC-α-LI were colocalized in rat retina, and thus all the bipolar cells with γ-ANP-LI were rod bipolar cells. In turtle, the γ-ANP antibody labeled certain bipolar cells that were characterized by bistratified axon terminals arborizing on the borders of strata S2/3 and S3/4 in the inner plexiform layer (IPL). Double labeling with PKC-α antibody indicated that bipolar cells with γ-ANP-LI were not the same bipolar cell types with PKC-α-LI. Thus, γ-ANP-LI appears to be a new marker for a distinct type of bipolar cell in turtle retina. At the ultrastructural level, the γ-ANP-LI was visible throughout the cytoplasm of the bipolar cells from dendrites to axon terminals. In the outer plexiform layer (OPL), labeled dendrites contacted photoreceptor pedicles almost exclusively at narrow-cleft basal junctions, but infrequently formed the central element at a photoreceptor ribbon synapse. In the IPL, axon terminals with γ-ANP-LI made ribbon synapses onto a combination of amacrine and ganglion cells. Since narrow-cleft basal junctions and photoreceptor ribbon-related junctions are known to be associated with ON-center bipolar cells in turtle, and since the axon terminals of bipolars with γ-ANP-LI stratify primarily in the ON-strata of the IPL, we suggest that these cells are likely to be ON-center cells. It is possible that the γ-ANP may be involved in regulating the activity of Na+/K+ ATPase or in the modulation of cGMP levels.

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García-Fandiño, Rebeca, Manuel Amorín, Luis Castedo, and Juan R. Granja. "Transmembrane ion transport by self-assembling α,γ-peptide nanotubes." Chemical Science 3, no. 11 (2012): 3280. http://dx.doi.org/10.1039/c2sc21068a.

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Liu, Lei, Li Ding, Matteo Rovere, Michael S. Wolfe, and Dennis J. Selkoe. "A cellular complex of BACE1 and γ-secretase sequentially generates Aβ from its full-length precursor." Journal of Cell Biology 218, no. 2 (January 9, 2019): 644–63. http://dx.doi.org/10.1083/jcb.201806205.

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Intramembrane proteolysis of transmembrane substrates by the presenilin–γ-secretase complex is preceded and regulated by shedding of the substrate’s ectodomain by α- or β-secretase. We asked whether β- and γ-secretases interact to mediate efficient sequential processing of APP, generating the amyloid β (Aβ) peptides that initiate Alzheimer’s disease. We describe a hitherto unrecognized multiprotease complex containing active β- and γ-secretases. BACE1 coimmunoprecipitated and cofractionated with γ-secretase in cultured cells and in mouse and human brain. An endogenous high molecular weight (HMW) complex (∼5 MD) containing β- and γ-secretases and holo-APP was catalytically active in vitro and generated a full array of Aβ peptides, with physiological Aβ42/40 ratios. The isolated complex responded properly to γ-secretase modulators. Alzheimer’s-causing mutations in presenilin altered the Aβ42/40 peptide ratio generated by the HMW β/γ-secretase complex indistinguishably from that observed in whole cells. Thus, Aβ is generated from holo-APP by a BACE1–γ-secretase complex that provides sequential, efficient RIP processing of full-length substrates to final products.

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DeLucia, Diana, Tiffany Pariva, Roland Strong, Owen Witte, and John Lee. "148 Identification of prostate-restricted epithelial antigens for transgenic T cell adoptive therapy against prostate cancer." Journal for ImmunoTherapy of Cancer 8, Suppl 3 (November 2020): A161. http://dx.doi.org/10.1136/jitc-2020-sitc2020.0148.

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BackgroundIn advanced prostate cancer (PCa), progression to castration-resistant PCa (CRPC) is inevitable and novel therapies for CRPC are needed. Adoptive transfer of T cells targeting tumor antigens is a promising approach in the cancer field. Unfortunately, identifying antigens expressed exclusively in prostate tumor cells has been challenging. Since the prostate is not an essential organ, we alternatively selected prostate-restricted epithelial antigens (PREAs) expressed in both malignant and normal prostate tissue for transgenic T cell studies.MethodsRNA-seq data sets identifying genes enriched in PCa were cross-referenced with the NIH Genotype-Expression database to identify PREAs. Using a novel molecular immunology approach, select PREAs and major histocompatibility complex class I (MHC-I) molecules were co-expressed in HEK293F cells, from which MHC–peptide complexes were efficiently isolated. Peptides were eluted and sequenced by mass spectrometry. Peptide–MHC binding was validated with a T2 stabilization assay and peptide immunodominance was determined using an interferon-γ (IFN-γ) ELISpot assay following stimulation of healthy HLA-A2+ peripheral blood mononuclear cells (PBMC) with peptide pools. Following peptide stimulation, CD8+ T cells with peptide-specific T cell receptors (TCR) were enriched by peptide–MHC-I dextramer labeling and fluorescence activated cell sorting for single cell TCR α/β chain sequencing.ResultsWe identified 11 A2+ peptides (8 previously unpublished) from prostatic acid phosphatase (ACPP), solute carrier family 45 member 3 (SLC45A3), and NK3 homeobox 1 (NKX3.1) that bound to HLA-A2 with varying affinities. Extended culture stimulation of PBMC with peptide pools from each PREA, compared to the standard overnight culture, revealed a greater number of IFN-γ producing cells overall and a greater breadth of response across all the peptides. Antigen specific CD8+ T cells were detectable at low frequencies in both male and female healthy PBMC for 7 of the 11 peptides. Dextramer-sorted antigen-specific cells were used for single-cell paired TCR αβ sequencing and transgenic T cell development.ConclusionsThrough this work we identified HLA-A2-presented antigenic peptides from the PREAs ACPP, SLC45A3, and NKX3.1 that can induce the expansion of IFN-γ producing CD8+ T cells. Through peptide–MHC-I dextramer labeling, we isolated PREA-specific CD8+ T cells and characterized TCR αβ sequences with potential anti-tumor functionality. Our results highlight a rapid and directed platform for the development of MHC-I-restricted transgenic CD8+ T cells targeting lineage-specific proteins expressed in prostate epithelia for adoptive therapy of advanced PCa.

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Shin, Young-Hee, and Hyunjun Yang. "Exploration of α/β/γ-peptidomimetics design for BH3 helical domains." Chemical Communications 58, no. 7 (2022): 945–48. http://dx.doi.org/10.1039/d1cc05758h.

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Domitrovic, Tatiana, Tsutomu Matsui, and John E. Johnson. "Dissecting Quasi-Equivalence in Nonenveloped Viruses: Membrane Disruption Is Promoted by Lytic Peptides Released from Subunit Pentamers, Not Hexamers." Journal of Virology 86, no. 18 (July 3, 2012): 9976–82. http://dx.doi.org/10.1128/jvi.01089-12.

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Nonenveloped viruses often invade membranes by exposing hydrophobic or amphipathic peptides generated by a proteolytic maturation step that leaves a lytic peptide noncovalently associated with the viral capsid. Since multiple copies of the same protein form many nonenveloped virus capsids, it is unclear if lytic peptides derived from subunits occupying different positions in a quasi-equivalent icosahedral capsid play different roles in host infection. We addressed this question withNudaurelia capensis omega virus(NωV), an insect RNA virus with an icosahedral capsid formed by protein α, which undergoes autocleavage during maturation, producing the lytic γ peptide. NωV is a unique model because autocatalysis can be precisely initiatedin vitroand is sufficiently slow to correlate lytic activity with γ peptide production. Using liposome-based assays, we observed that autocatalysis is essential for the potent membrane disruption caused by NωV. We observed that lytic activity is acquired rapidly during the maturation program, reaching 100% activity with less than 50% of the subunits cleaved. Previous time-resolved structural studies of partially mature NωV particles showed that, during this time frame, γ peptides derived from the pentamer subunits are produced and are organized in a vertical helical bundle that is projected toward the particle surface, while identical polypeptides in quasi-equivalent subunits are produced later or are in positions inappropriate for release. Our functional data provide experimental support for the hypothesis that pentamers containing a central helical bundle, observed in different nonenveloped virus families, are a specialized lytic motif.

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Lenz, Derek C., Norbert A. Wolf, and Robert H. Swanborg. "Strain Variation in Autoimmunity: Attempted Tolerization of DA Rats Results in the Induction of Experimental Autoimmune Encephalomyelitis." Journal of Immunology 163, no. 4 (August 15, 1999): 1763–68. http://dx.doi.org/10.4049/jimmunol.163.4.1763.

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Abstract This paper reports that DA rats develop experimental autoimmune encephalomyelitis (EAE) when immunized with encephalitogenic myelin basic protein (MBP) peptide (MBP63–81) in IFA. In contrast, most rodent strains are tolerized by this procedure. Doses as low as 5 μg peptide + IFA induced EAE in DA rats. Lewis (LEW) rats did not develop EAE, even after immunization with 100 μg encephalitogenic peptide (MBP68–86) + IFA, but were rendered tolerant to EAE. DA rat T cells proliferated to peptide, and proliferation was inhibited by CTLA4Ig, and by anti-B7.1 and anti-B7.2 mAbs. This indicates that the ease of induction of EAE in this strain does not reflect a decreased requirement for T cell costimulation through the B7/CD28 costimulatory pathway. The inhibitory effect of CTLA4Ig was abrogated in the presence of anti-TGF-β-neutralizing Ab. An encephalitogenic DA T cell line expressed mRNA for the Th1 cytokines IFN-γ and TNF-α, as well as IL-10, and secreted these cytokines. In contrast, a T cell line from peptide + IFA-immunized LEW rats (which did not develop EAE) failed to secrete these cytokines. Although this line did not express TNF-α or IL-10 mRNA, IFN-γ mRNA was detected, suggesting posttranscriptional regulation of IFN-γ expression. Attempts to induce unresponsiveness in DA rats with encephalitogenic peptide-coupled splenocytes were also unsuccessful.

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Humphreys, Michael H. "γ-MSH, sodium metabolism, and salt-sensitive hypertension." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 286, no. 3 (March 2004): R417—R430. http://dx.doi.org/10.1152/ajpregu.00365.2003.

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α-, β-, and γ-melanocyte stimulating hormones (MSHs) are melanotropin peptides that are derived from the ACTH/β-endorphin prohormone proopiomelanocortin (POMC). They have been highly conserved through evolutionary development, although their functions in mammals have remained obscure. The identification in the last decade of a family of five membrane-spanning melanocortin receptors (MC-Rs), for which the melanotropins are the natural ligands, has permitted the characterization of a number of important actions of these peptides, although the physiological function(s) of γ-MSH have remained elusive. Much evidence indicates that γ-MSH stimulates sympathetic outflow and raises blood pressure through a central mechanism. However, this review focuses on newer cardiovascular and renal actions of the peptide, acting in most cases through the MC3-R. In rodents, a high-sodium diet (HSD) increases the pituitary abundance of POMC mRNA and of γ-MSH content and results in a doubling of plasma γ-MSH concentration. The peptide is natriuretic and acts through renal MC3-Rs, which are also upregulated by the HSD. Thus the system appears designed to participate in the integrated response to dietary sodium excess. Genetic or pharmacologic induction of γ-MSH deficiency results in marked salt-sensitive hypertension that is corrected by the administration of the peptide, probably through a central site of action. Deletion of the MC3-R also produces salt-sensitive hypertension, which, however, is not corrected by infusion of the hormone. These observations in aggregate suggest the operation of a hormonal system important in blood pressure control and in the regulation of sodium excretion. The relationship of these two actions to each other and the significance of this system in humans are important questions for future research.

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van der Veken, Lars T., Renate S. Hagedoorn, Marleen M. van Loenen, Roel Willemze, J. H. Frederik Falkenburg, and Mirjam H. M. Heemskerk. "Re-Engineering γ δ T Cells by α β T Cell Receptor Gene Transfer Creates Potent Effector Cells with Anti-Leukemic Reactivity." Blood 106, no. 11 (November 16, 2005): 1288. http://dx.doi.org/10.1182/blood.v106.11.1288.1288.

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Abstract Retroviral transfer of T cell receptors (TCRs) to peripheral blood derived T cells generates large numbers of T cells with the same antigen specificity, which can potentially be used for adoptive immunotherapy. One drawback of this procedure is the formation of mixed α β TCR dimers with unknown specificities due to pairing of endogenous and introduced TCR chains. To completely prevent the formation of mixed TCR dimers by TCR gene transfer to α β T cells we investigated whether γ δ T cells can serve as alternative host T cells for α β TCR transfer, since the γ δ TCR is not capable of forming dimers with the α β TCR. Peripheral blood derived γ δT cells were isolated by immunomagnetic bead isolation and subsequent FACS sorting, resulting in >99% pure populations of γ δT cells. The isolated γ δT cells were retrovirally transduced with three different TCRs specific for the hematopoietic minor histocompatibility antigen (mHag) HA-2 in the context of HLA-A2, for CMV-pp65 in the context of HLA-B7, or for the HLA class II restricted mHag DBY. The TCR-transduced γ δT cells expressed both the introduced TCRs and the endogenous γ δTCR at their cell surface as determined by FACS analysis. When γ δT cells transduced with the HLA class I restricted HA-2-TCR or CMV-TCR were stained with tetramers, only the CMV-TCR expressing γ δT cells but not the HA-2-TCR expressing γ δT cells were capable of strong antigen specific tetramer binding. In contrast, functional analysis indicated that all TCR-transduced γ δT cells specifically recognized peptide pulsed target cells leading to target cell lysis and IFNγ and IL-4 production, indicating that while the avidity of the HA-2-TCR engineered γ δT cells was insufficient for strong antigen specific tetramer binding, the avidity was high enough for the specific recognition of peptide pulsed target cells. However, the functional reactivity of the TCR-transduced γ δT cells against target cells presenting endogenously processed antigens was low. FACS analysis indicated that most γ δT cells lacked the expression of the coreceptors CD4 and CD8. Therefore, we investigated whether introduction of the relevant coreceptor could enhance the functionality of the redirected γ δT cells. Co-transfer of the CD8α β coreceptor to the HA-2-TCR and CMV-TCR transferred γ δT cells turned them into effective, antigen specific tetramer binders. Furthermore, expression of CD8α β by the HA-2-TCR and CMV-TCR transduced γ δT cells and CD4 by the DBY-TCR transduced γ δT cells generated powerful effector cells exerting high levels of antigen specific lysis of both peptide pulsed target cells and target cells presenting endogenously processed antigen. In addition, coreceptor expressing TCR-engineered γ δT cells produced high amounts of IFNγ and IL-4 when stimulated with peptide pulsed target cells or endogenously processed antigen. To investigate the anti-leukemic reactivity of TCR-transferred γ δT cells, we determined the antigen specific cytotoxicity and cytokine production against primary CML and AML cells by γ δT cells equipped with the HA-2-TCR and CD8α β . We observed both antigen specific cytolytic activity and cytokine production against both CML and AML cells expressing the hematopoiesis specific mHag HA-2, while HLA-A2+ leukemic cells lacking expression of the HA-2 mHag were not recognized. These data demonstrate that transfer of α β TCRs to γ δT cells generated potent effector cells for immunotherapy of leukemia, without the expression of potentially hazardous mixed TCR dimers.

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Karin, Nathan, Ofer Binah, Nir Grabie, Dennis J. Mitchell, Bella Felzen, Matthew D. Solomon, Paul Conlon, Amitabh Gaur, Nicholas Ling, and Lawrence Steinman. "Short Peptide-Based Tolerogens Without Self-Antigenic or Pathogenic Activity Reverse Autoimmune Disease." Journal of Immunology 160, no. 10 (May 15, 1998): 5188–94. http://dx.doi.org/10.4049/jimmunol.160.10.5188.

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Abstract An immunodominant epitope of myelin basic protein (MBP), VHFFKNIVTPRTP (p87–99), is a major target of T cells in brain lesions of multiple sclerosis (MS), and this peptide can trigger experimental autoimmune encephalomyelitis (EAE). We designed truncated peptides based on this pathogenic 13-mer that are not antigenic. These short peptides reduced production of IFN-γ and TNF-α in vivo. Moreover, paraplegic rats given the 7-mer FKNIVTP in soluble form showed total reversal of paralysis in 24 h. Truncated peptides that are too small to stimulate antigenic responses to pathogenic regions of myelin basic protein are nevertheless effective tolerogens and are able to anergize autoreactive T cells. Short peptide-based tolerogens, devoid of immunogenic and pathogenic potential, may be attractive for therapy of autoimmune diseases.

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Reiriz, César, Roberto J. Brea, Rocío Arranz, José L. Carrascosa, Alejandra Garibotti, Brendan Manning, José M. Valpuesta, Ramón Eritja, Luis Castedo, and Juan R. Granja. "α,γ-Peptide Nanotube Templating of One-Dimensional Parallel Fullerene Arrangements." Journal of the American Chemical Society 131, no. 32 (August 19, 2009): 11335–37. http://dx.doi.org/10.1021/ja904548q.

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Fuertes, Alberto, Manuel Amorín, and Juan R. Granja. "Membrane spanners based on a dimeric α,γ-cyclic peptide core." Supramolecular Chemistry 32, no. 4 (February 27, 2020): 239–46. http://dx.doi.org/10.1080/10610278.2020.1731510.

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Kuo, Lan-Hsin, Ming-Kuan Hu, Wen-Ming Hsu, Ying-Tsen Tung, Bo-Jeng Wang, Wang-Wei Tsai, Chen-Tung Yen, and Yung-Feng Liao. "Tumor Necrosis Factor-α–elicited Stimulation of γ-Secretase Is Mediated by c-Jun N-terminal Kinase-dependent Phosphorylation of Presenilin and Nicastrin." Molecular Biology of the Cell 19, no. 10 (October 2008): 4201–12. http://dx.doi.org/10.1091/mbc.e07-09-0987.

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γ-Secretase is a multiprotein complex composed of presenilin (PS), nicastrin (NCT), Aph-1, and Pen-2, and it catalyzes the final proteolytic step in the processing of amyloid precursor protein to generate amyloid-β. Our previous results showed that tumor necrosis factor-α (TNF-α) can potently stimulate γ-secretase activity through a c-Jun N-terminal kinase (JNK)-dependent pathway. Here, we demonstrate that TNF-α triggers JNK-dependent serine/threonine phosphorylation of PS1 and NCT to stimulate γ-secretase activity. Blocking of JNK activity with a potent JNK inhibitor (SP600125) reduces TNF-α–triggered phosphorylation of PS1 and NCT. Consistent with this, we show that activated JNKs can be copurified with γ-secretase complexes and that active recombinant JNK2 can promote the phosphorylation of PS1 and NCT in vitro. Using site-directed mutagenesis and a synthetic peptide, we clearly show that the Ser319Thr320 motif in PS1 is an important JNK phosphorylation site that is critical for the TNF-α–elicited regulation of γ-secretase. This JNK phosphorylation of PS1 at Ser319Thr320 enhances the stability of the PS1 C-terminal fragment that is necessary for γ-secretase activity. Together, our findings strongly suggest that JNK is a critical intracellular mediator of TNF-α–elicited regulation of γ-secretase and governs the pivotal step in the assembly of functional γ-secretase.

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Barre, Annick, Hervé Benoist, and Pierre Rougé. "Impacts of Sourdough Technology on the Availability of Celiac Peptides from Wheat α- and γ-Gliadins: In Silico Approach." Allergies 3, no. 1 (February 3, 2023): 39–57. http://dx.doi.org/10.3390/allergies3010004.

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Celiac peptide-generating α- and γ-gliadins consist of a disordered N-terminal domain extended by an α-helical-folded C-terminal domain. Celiac peptides, primarily located along the disordered part of α- and γ-gliadin molecules, are nicely exposed and directly accessible to proteolytic enzymes occurring in the gastric (pepsin) and intestinal (trypsin, chymotrypsin) fluids. More than half of the potential celiac peptides identified so far in gliadins exhibit cleavage sites for pepsin. However, celiac peptides proteolytically truncated by one or two amino acid residues could apparently retain some activity toward HLA-DQ2 and HLA-DQ8 receptors in docking experiments. Together with the uncleaved peptides, these still active partially degraded CD peptides account for the incapacity of the digestion process to inactivate CD peptides from gluten proteins. In contrast, sourdough fermentation processes involve other proteolytic enzymes susceptible to the deep degradation of celiac peptides. In particular, sourdough supplemented by fungal prolyl endoproteases enhances the degrading capacities of the sourdough fermentation process toward celiac peptides. Nevertheless, since tiny amounts of celiac peptides sufficient to trigger deleterious effects on CD people can persist in sourdough-treated bread and food products, it is advisable to avoid consumption of sourdough-treated food products for people suffering from celiac disease. As an alternative, applying the supplemented sourdough process to genetically modified low gluten or celiac-safe wheat lines should result in food products that are safer for susceptible and CD people.

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Abdelbaky, Ahmed S., Ivan A. Prokhorov, Igor P. Smirnov, Kristina M. Koroleva, Vitaliy I. Shvets, and Yulia G. Kirillova. "Synthesis of α-(R)-/γ-(S)-Dimethyl Substituted Peptide Nucleic Acid Submonomer Using Mitsunobu Reaction." Letters in Organic Chemistry 16, no. 5 (April 1, 2019): 437–46. http://dx.doi.org/10.2174/1570178616666190118155031.

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One of the major challenges facing modern biochemical and biomedical technologies are finding molecular tools for diagnosis and detection of genetic diseases. In this connection, several classes of oligonucleotides have been developed that can recognize and bind to DNA and RNA with high affinity and sequence selectivity and withstand enzymatic degradation by proteases and nucleases; however, few can traverse the cell membrane on their own. One such promising class of nucleic acid mimics developed in the last two decades which showed good results in vitro, are the peptide nucleic acids (PNAs). New chiral α- and γ-peptide Nucleic Acid (PNA) submonomer with methyl substituents in pseudopeptide backbone were synthesized via Mitsunobu reaction. The α-(R)-/γ-(S)-configuration of the chiral centres will ensure the preorganization of the PNA oligomer into a right-handed helix. The results obtained showed that Boc/Fmoc-submonomer compatible with Boc-protocol PNAs solid-phase synthesis on an MBHA resin. We synthesized simple and efficient α-R-, γ-S-disubstituted PNA submonomer based on L-Ala and D-Ala with the construction of the intermediate pseudopeptide moiety by Mitsunobu reaction for subsequent use in the Boc-Protocol of solid phase PNA synthesis.

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Al-Attiyah, R., and A. S. Mustafa. "Characterization of Human Cellular Immune Responses to Novel Mycobacterium tuberculosis Antigens Encoded by Genomic Regions Absent in Mycobacterium bovis BCG." Infection and Immunity 76, no. 9 (June 23, 2008): 4190–98. http://dx.doi.org/10.1128/iai.00199-08.

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ABSTRACT Comparative genomics has identified several regions of differences (RDs) between the infectious Mycobacterium tuberculosis and the vaccine strains of Mycobacterium bovis BCG. We aimed to evaluate the cellular immune responses induced by antigens encoded by genes predicted in 11 RDs. Synthetic peptides covering the sequences of RD1, RD4 to RD7, RD9 to RD13, and RD15 were tested for antigen-induced proliferation and secretion of Th1 cytokine, gamma interferon (IFN-γ), by peripheral blood mononuclear cells (PBMC) obtained from culture-proven pulmonary tuberculosis (TB) patients and M. bovis BCG-vaccinated healthy subjects. Among the peptide pools, RD1 induced the best responses in both donor groups and in both assays. In addition, testing of TB patients' PBMC for secretion of proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin 6 [IL-6], IL-8, and IL-1β), Th1 cytokines (IFN-γ, IL-2, and TNF-β), and Th2 cytokines (IL-4, IL-5, and IL-10) showed differential effects of RD peptides in the secretion of IFN-γ and IL-10, with high IFN-γ/IL-10 ratios (32 to 5.0) in response to RD1, RD5, RD7, RD9, and RD10 and low IFN-γ/IL-10 ratios (<1.0) in response to RD12, RD13, and RD15. Peptide-mixing experiments with PBMC from healthy subjects showed that secretion of large quantities of IL-10 in response to RD12 and RD13 correlated with inhibition of Th1 responses induced by RD1 peptides. In conclusion, our results suggest that M. tuberculosis RDs can be divided into two major groups—one group that activates PBMC to preferentially secrete IFN-γ and another group that activates preferential secretion of IL-10—and that these two groups of RDs may have roles in protection against and pathogenesis of TB, respectively.

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Lewicki, Hanna, Antoinette Tishon, Dirk Homann, Honoré Mazarguil, Françoise Laval, Valerie C. Asensio, Iain L. Campbell, et al. "T Cells Infiltrate the Brain in Murine and Human Transmissible Spongiform Encephalopathies." Journal of Virology 77, no. 6 (March 15, 2003): 3799–808. http://dx.doi.org/10.1128/jvi.77.6.3799-3808.2003.

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ABSTRACT CD4 and CD8 T lymphocytes infiltrate the parenchyma of mouse brains several weeks after intracerebral, intraperitoneal, or oral inoculation with the Chandler strain of mouse scrapie, a pattern not seen with inoculation of prion protein knockout (PrP−/−) mice. Associated with this cellular infiltration are expression of MHC class I and II molecules and elevation in levels of the T-cell chemokines, especially macrophage inflammatory protein 1β, IFN-γ-inducible protein 10, and RANTES. T cells were also found in the central nervous system (CNS) in five of six patients with Creutzfeldt-Jakob disease. T cells harvested from brains and spleens of scrapie-infected mice were analyzed using a newly identified mouse PrP (mPrP) peptide bearing the canonical binding motifs to major histocompatibility complex (MHC) class I H-2b or H-2d molecules, appropriate MHC class I tetramers made to include these peptides, and CD4 and CD8 T cells stimulated with 15-mer overlapping peptides covering the whole mPrP. Minimal to modest Kb tetramer binding of mPrP amino acids (aa) 2 to 9, aa 152 to 160, and aa 232 to 241 was observed, but such tetramer-binding lymphocytes as well as CD4 and CD8 lymphocytes incubated with the full repertoire of mPrP peptides failed to synthesize intracellular gamma interferon (IFN-γ) or tumor necrosis factor alpha (TNF-α) cytokines and were unable to lyse PrP−/− embryo fibroblasts or macrophages coated with 51Cr-labeled mPrP peptide. These results suggest that the expression of PrPsc in the CNS is associated with release of chemokines and, as shown previously, cytokines that attract and retain PrP-activated T cells and, quite likely, bystander activated T cells that have migrated from the periphery into the CNS. However, these CD4 and CD8 T cells are defective in such an effector function(s) as IFN-γ and TNF-α expression or release or lytic activity.

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Tran, Oanh, Silke Kerruth, Catherine Coates, Hansween Kaur, Camillo Peracchia, Tom Carter, and Katalin Török. "Ca2+-Dependent and -Independent Calmodulin Binding to the Cytoplasmic Loop of Gap Junction Connexins." International Journal of Molecular Sciences 24, no. 4 (February 19, 2023): 4153. http://dx.doi.org/10.3390/ijms24044153.

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Ca2+/calmodulin (Ca2+/CaM) interaction with connexins (Cx) is well-established; however, the mechanistic basis of regulation of gap junction function by Ca2+/CaM is not fully understood. Ca2+/CaM is predicted to bind to a domain in the C-terminal portion of the intracellular loop (CL2) in the vast majority of Cx isoforms and for a number of Cx-s this prediction has proved correct. In this study, we investigate and characterise both Ca2+/CaM and apo-CaM binding to selected representatives of each of the α, β and γ connexin family to develop a better mechanistic understanding of CaM effects on gap junction function. The affinity and kinetics Ca2+/CaM and apo-CaM interactions of CL2 peptides of β-Cx32, γ-Cx35, α-Cx43, α-Cx45 and α-Cx57 were investigated. All five Cx CL2 peptides were found to have high affinity for Ca2+/CaM with dissociation constants (Kd(+Ca)) from 20 to 150 nM. The limiting rate of binding and the rates of dissociation covered a broad range. In addition, we obtained evidence for high affinity Ca2+-independent interaction of all five peptides with CaM, consistent with CaM remaining anchored to gap junctions in resting cells. However, for the α-Cx45 and α-Cx57 CL2 peptides, Ca2+-dependent association at resting [Ca2+] of 50–100 nM is indicated in these complexes as one of the CaM Ca2+ binding sites displays high affinity with Kd of 70 and 30 nM for Ca2+, respectively. Furthermore, complex conformational changes were observed in peptide-apo-CaM complexes with the structure of CaM compacted or stretched by the peptide in a concentration dependent manner suggesting that the CL2 domain may undergo helix-to-coil transition and/or forms bundles, which may be relevant in the hexameric gap junction. We demonstrate inhibition of gap junction permeability by Ca2+/CaM in a dose dependent manner, further cementing Ca2+/CaM as a regulator of gap junction function. The motion of a stretched CaM–CL2 complex compacting upon Ca2+ binding may bring about the Ca2+/CaM block of the gap junction pore by a push and pull action on the CL2 C-terminal hydrophobic residues of transmembrane domain 3 (TM3) in and out of the membrane.

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Hooper, N. M. "Roles of proteolysis and lipid rafts in the processing of the amyloid precursor protein and prion protein." Biochemical Society Transactions 33, no. 2 (April 1, 2005): 335–38. http://dx.doi.org/10.1042/bst0330335.

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In the amyloidogenic pathway, the APP (amyloid precursor protein) is proteolytically processed by the β- and γ-secretases to release the Aβ (amyloid-β) peptide that is neurotoxic and aggregates in the brains of patients suffering from Alzheimer's disease. In the non-amyloidogenic pathway, APP is cleaved by α-secretase within the Aβ domain, precluding deposition of intact Aβ peptide. The cellular form of the PrPC (prion protein) undergoes reactive oxygen species-mediated β-cleavage within the copper-binding octapeptide repeats or, alternatively, α-cleavage within the central hydrophobic neurotoxic domain. In addition, PrPC is shed from the membrane by the action of a zinc metalloprotease. Members of the ADAM (a disintegrin and metalloproteinase) family of zinc metalloproteases, notably ADAM10 and TACE (ADAM17) display α-secretase activity towards APP and appear to be responsible for the α-cleavage of PrPC. The amyloidogenic cleavage of APP by the β- and γ-secretases appears to occur preferentially in cholesterol-rich lipid rafts, while the conversion of PrPC into the infectious form PrPSc also appears to occur in these membrane domains.

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Fisher, Brian F., and Samuel H. Gellman. "Impact of γ-Amino Acid Residue Preorganization on α/γ-Peptide Foldamer Helicity in Aqueous Solution." Journal of the American Chemical Society 138, no. 34 (August 16, 2016): 10766–69. http://dx.doi.org/10.1021/jacs.6b06177.

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Schedel, Hartmut, Wojciech Dmowski, and Klaus Burger. "New Stereoconservative Syntheses of β,β,β- and γ,γ,γ-Trifluoro-α-amino, α-Hydroxy, and α-Mercapto Acids and Their Incorporation into a Peptide and Depsipeptide Fragment." Synthesis 2000, no. 12 (2000): 1681–88. http://dx.doi.org/10.1055/s-2000-8198.

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Calvelo, Martín, Saulo Vázquez, and Rebeca García-Fandiño. "Molecular dynamics simulations for designing biomimetic pores based on internally functionalized self-assembling α,γ-peptide nanotubes." Physical Chemistry Chemical Physics 17, no. 43 (2015): 28586–601. http://dx.doi.org/10.1039/c5cp04200c.

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Internally functionalized peptide nanotubes composed of α- and γ-amino acids self assembled in lipid bilayers are studied using Molecular Dynamics simulations, projecting a promising future for their use as biomimetic channels when properly innerderivatized.

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Ramaswami, Bala, Iulia Popescu, Camila Macedo, Chunqing Luo, Ron Shapiro, Diana Metes, Geetha Chalasani, and Parmjeet S. Randhawa. "The Polyomavirus BK Large T-Antigen-Derived Peptide Elicits an HLA-DR Promiscuous and Polyfunctional CD4+T-Cell Response." Clinical and Vaccine Immunology 18, no. 5 (March 2, 2011): 815–24. http://dx.doi.org/10.1128/cvi.00487-10.

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ABSTRACTBK virus (BKV) nephropathy and hemorrhagic cystitis are increasingly recognized causes of disease in renal and hematopoietic stem cell transplant recipients, respectively. Functional characterization of the immune response to BKV is important for clinical diagnosis, prognosis, and vaccine design. A peptide mix (PepMix) and overlapping (OPP) or random (RPP) peptide pools derived from BKV large T antigen (LTA) were used to restimulate 14-day-expanded peripheral blood mononuclear cells (PBMC) from 27 healthy control subjects in gamma interferon (IFN-γ)-specific enzyme-linked immunospot (ELISPOT) assays. A T-cell response to LTA PepMix was detected in 15/27 subjects. A response was frequently observed with peptides derived from the helicase domain (9/15 subjects), while the DNA binding and host range domains were immunologically inert (0/15 subjects). For all nine subjects who responded to LTA peptide pools, the immune response could be explained largely by a 15-mer peptide designated P313. P313-specific CD4+T-cell clones demonstrated (i) stringent LTA peptide specificity; (ii) promiscuous recognition in the context of HLA-DR alleles; (iii) cross recognition of homologous peptides from the polyomavirus simian virus 40 (SV40); (iv) an effector memory phenotype, CD107a expression, and intracellular production of IFN-γ and tumor necrosis factor alpha (TNF-α); (v) cytotoxic activity in a chromium release assay; and (vi) the ability to directly present cognate antigen to autologous T cells. In conclusion, T-cell-mediated immunity to BKV in healthy subjects is associated with a polyfunctional population of CD4+T cells with dual T-helper and T-cytotoxic properties. HLA class II promiscuity in antigen presentation makes the targeted LTA peptide sequence a suitable candidate for inclusion in immunotherapy protocols.

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Aleanzi, Mabel, Ana María Demonte, Cecilia Esper, Silvia Garcilazo, and Marta Waggener. "Celiac Disease." Clinical Chemistry 47, no. 11 (November 1, 2001): 2023–28. http://dx.doi.org/10.1093/clinchem/47.11.2023.

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Abstract Background: Selective deamidation of glutamine residues by tissue transglutaminase (tTG) turns gliadin peptides into stronger activators of T cells from celiac disease (CD) patients. We examined the possibility that these modified peptides could be more specific epitopes for circulating antibodies than are native peptides. Methods: Two native synthetic peptides and their respective modified sequences were used as antigens for ELISA assays: peptide-1, with residues 56–75 of α-type gliadin; and peptide-2, with residues 134–153 of γ-type gliadin. We examined 40 CD patients [31 not being treated with a gluten-free diet (GFD) and 9 being treated with a GFD] and 30 non-CD patients. Results: An enhanced response against deamidated peptides was observed in 4 (IgA) and 22 (IgG) of 31 untreated CD patients for peptide-1 and in 25 (IgA) and 29 (IgG) patients for peptide-2. Higher anti-gliadin antibody and anti-tTG IgA concentrations correlated with increased IgA reactivity to modified peptides. Among the nine treated CD patients, eight also displayed an improved IgG signal for the deamidated sequence. Deamidation of peptides did not increase the reactivity of non-CD sera. Conclusions: Selective deamidation specifically increases circulating antibody recognition of gliadin peptides in CD patients. This suggests that deamidated gliadin peptides are more specific CD B-cell epitopes than native peptides; this finding may be relevant for designing improved diagnostic tests.

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Kanda, Naoko, and Shinichi Watanabe. "Histamine enhances the production of human β-defensin-2 in human keratinocytes." American Journal of Physiology-Cell Physiology 293, no. 6 (December 2007): C1916—C1923. http://dx.doi.org/10.1152/ajpcell.00293.2007.

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The anti-microbial peptide human β-defensin-2 (hBD-2), produced by epidermal keratinocytes, plays pivotal roles in anti-microbial defense, inflammatory dermatoses, and wound repair. hBD-2 induces histamine release from mast cells. We examined the in vitro effects of histamine on hBD-2 production in normal human keratinocytes. Histamine enhanced TNF-α- or IFN-γ-induced hBD-2 secretion and mRNA expression. Histamine alone enhanced transcriptional activities of NF-κB and activator protein-1 (AP-1) and potentiated TNF-α-induced NF-κB and AP-1 activities or IFN-γ-induced NF-κB and STAT1 activities. Antisense oligonucleotides against NF-κB components p50 and p65, AP-1 components c-Jun and c-Fos, or H1 antagonist pyrilamine suppressed hBD-2 production induced by histamine plus TNF-α or IFN-γ. Antisense oligonucleotide against STAT1 only suppressed hBD-2 production induced by histamine plus IFN-γ. Histamine induced serine phosphorylation of inhibitory NF-κBα (IκBα) alone or together with TNF-α or IFN-γ. Histamine induced c-Fos mRNA expression alone or together with TNF-α, whereas it did not further increase c-Jun mRNA levels enhanced by TNF-α. Histamine induced serine phosphorylation of STAT1 alone or together with IFN-γ, whereas it did not further enhance IFN-γ-induced tyrosine phosphorylation of STAT1. The histamine-induced serine phosphorylation of STAT1 was suppressed by MAPKK (MEK) inhibitor PD98059. These results suggest that histamine stimulates H1 receptor and potentiates TNF-α- or IFN-γ-induced hBD-2 production dependent on NF-κB, AP-1, or STAT1 in human keratinocytes. Histamine may potentiate anti-microbial defense, skin inflammation, and wound repair via the induction of hBD-2.

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Journal articles on the topic 'Α/γ Peptide'

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