Academic literature on the topic 'Α/β Peptide'
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Journal articles on the topic "Α/β Peptide"
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Checco, James W., Dale F. Kreitler, Nicole C. Thomas, David G. Belair, Nicholas J. Rettko, William L. Murphy, Katrina T. Forest, and Samuel H. Gellman. "Targeting diverse protein–protein interaction interfaces with α/β-peptides derived from the Z-domain scaffold." Proceedings of the National Academy of Sciences 112, no. 15 (March 30, 2015): 4552–57. http://dx.doi.org/10.1073/pnas.1420380112.
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Peptide-based agents derived from well-defined scaffolds offer an alternative to antibodies for selective and high-affinity recognition of large and topologically complex protein surfaces. Here, we describe a strategy for designing oligomers containing both α- and β-amino acid residues (“α/β-peptides”) that mimic several peptides derived from the three-helix bundle “Z-domain” scaffold. We show that α/β-peptides derived from a Z-domain peptide targeting vascular endothelial growth factor (VEGF) can structurally and functionally mimic the binding surface of the parent peptide while exhibiting significantly decreased susceptibility to proteolysis. The tightest VEGF-binding α/β-peptide inhibits the VEGF165-induced proliferation of human umbilical vein endothelial cells. We demonstrate the versatility of this strategy by showing how principles underlying VEGF signaling inhibitors can be rapidly extended to produce Z-domain–mimetic α/β-peptides that bind to two other protein partners, IgG and tumor necrosis factor-α. Because well-established selection techniques can identify high-affinity Z-domain derivatives from large DNA-encoded libraries, our findings should enable the design of biostable α/β-peptides that bind tightly and specifically to diverse targets of biomedical interest. Such reagents would be useful for diagnostic and therapeutic applications.
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Oppegård, Camilla, Gunnar Fimland, Lisbeth Thorbæk, and Jon Nissen-Meyer. "Analysis of the Two-Peptide Bacteriocins Lactococcin G and Enterocin 1071 by Site-Directed Mutagenesis." Applied and Environmental Microbiology 73, no. 9 (March 2, 2007): 2931–38. http://dx.doi.org/10.1128/aem.02718-06.
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ABSTRACT The two peptides (Lcn-α and Lcn-β) of the two-peptide bacteriocin lactococcin G (Lcn) were changed by stepwise site-directed mutagenesis into the corresponding peptides (Ent-α and Ent-β) of the two-peptide bacteriocin enterocin 1071 (Ent), and the potencies and specificities of the various hybrid constructs were determined. Both Lcn and, to a lesser extent, Ent were active against all the tested lactococcal strains, but only Ent was active against the tested enterococcal strains. The two bacteriocins thus differed in their relative potencies to various target cells, despite their sequence similarities. The hybrid combination Lcn-α+Ent-β had low potency against all strains tested, indicating that these two peptides do not interact optimally. The reciprocal hybrid combination (i.e., Ent-α+Lcn-β), in contrast, was highly potent, indicating that these two peptides may form a functional antimicrobial unit. In fact, this hybrid combination (Ent-α+Lcn-β) was more potent against lactococcal strains than wild-type Ent was (i.e., Ent-α+Ent-β), but it was inactive against enterococcal strains (in contrast to Ent but similar to Lcn). The observation that Ent-α is more active against lactococci in combination with Lcn-β and more active against enterococci in combination with Ent-β suggests that the β peptide is an important determinant of target cell specificity. Especially the N-terminal residues of the β peptide seem to be important for specificity, since Ent-α combined with an Ent-β variant with Ent-to-Lcn mutations at positions 1 to 4, 7, 9, and 10 was >150-fold less active against enterococcal strains but one to four times more active against lactococcal strains than Ent-α+Ent-β. Moreover, Ent-to-Lcn single-residue mutations in the region spanning residues 1 to 7 in Ent-β had a more detrimental effect on the activity against enterococci than on that against lactococcal strains. Of the single-residue mutations made in the N-terminal region of the α peptide, the Ent-to-Lcn mutations N8Q and P12R in Ent-α influenced specificity, as follows: the N8Q mutation had no effect on activity against tested enterococcal strains but increased the activity 2- to 4-fold against the tested lactococcal strains, and the P12R mutation reduced the activity >150-fold and only ∼2-fold against enterococcal and lactococcal strains, respectively. Changing residues in the C-terminal half/part of the Lcn peptides (residues 20 to 39 and 25 to 35 in Lcn-α and Lcn-β, respectively) to those found in the corresponding Ent peptides did not have a marked effect on the activity, but there was an ∼10-fold or greater reduction in the activity upon also introducing Lcn-to-Ent mutations in the mid-region (residues 8 to 19 and 9 to 24 in Lcn-α and Lcn-β, respectively). Interestingly, the Lcn-to-Ent F19L+G20A mutation in an Lcn-Ent-β hybrid peptide was more detrimental when the altered peptide was combined with Lcn-α (>10-fold reduction) than when it was combined with Ent-α (∼2-fold reduction), suggesting that residues 19 and 20 (which are part of a GXXXG motif) in the β peptide may be involved in a specific interaction with the cognate α peptide. It is also noteworthy that the K2P and A7P mutations in Lcn-β reduced the activity only ∼2-fold, suggesting that the first seven residues in the β peptides do not form an α-helix.
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Fox, Robert I., and Ho-Il Kang. "Mechanism of Action of Antimalarial Drugs: Inhibition of Antigen Processing and Presentation." Lupus 2, no. 1_suppl (February 1993): 9–12. http://dx.doi.org/10.1177/0961203393002001031.
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Recent studies have elucidated the steps involved in the association of antigenic peptides with major histocompatibility complex (MHC) encoded proteins and have suggested how antimalarial compounds might influence this important site of immune activation. These steps of antigen presentation in the macrophage (or other antigen-presenting cells) include: (a) the partial proteolytic degradation of endogenous and exogenous proteins into peptides within the lysosome; (b) the synthesis of MHC class II (i.e. HLA-D associated) α, β, and invariant (Ii) chains in the endoplasmic reticulum; (c) the initial association of α-Ii and β-li chains in the endoplasmic reticulum and the transport of these complexes to the primary endosome; (d) the fusion of lysosomal vacuoles and endosomal vacuoles, allowing the mixtures of lysosomal enzymes, peptides, α–Ii and β–Ii; (e) the displacement of Ii chains by peptides to form α–β–peptide complexes in the endosome; and (f) the migration of α–β–peptide complexes to the macrophage cell surface where they can stimulate CD4 T cells, resulting in release of cytokines. A low pH is required for digestion of the protein by acidic hydrolases in the lysosome, for assembly of the α–β–peptide complex and for its transport to the cell surface. Chloroquine and hydroxychloroquine are weak diprotic bases that can diffuse across the cell membrane and raise the pH within cell vesicles. This background provides the underlying basis for the theory that antimalarials may act to prevent autoimmunity by the following putative mechanism. Antimalarial compounds may: (a) stabilize the α-Ii and β-Ii interactions and prevent low-affinity peptides from forming α–β–peptide complexes; and (b) interfere with the efficient movement of α-Ii, β-Ii and α–β–peptide complexes to the correct locations within the cell cytoplasm or to the cell surfaces. Decreased presentation of autoantigenic peptides by macrophages might then lead to downregulation of autoimmune CD4+ T cells and diminish release of cytokines associated with clinical and laboratory signs of autoimmune disease.
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Maruthainar, K., Y. Peng-Loh, and D. G. Smyth. "The processing of β-endorphin and α-melanotrophin in the pars intermedia of Xenopus laevis is influenced by background adaptation." Journal of Endocrinology 135, no. 3 (December 1992): 469–78. http://dx.doi.org/10.1677/joe.0.1350469.
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ABSTRACT β-Endorphin-and α-melanotrophin (α-MSH)-related peptides were extracted from the pars intermedia of Xenopus laevis maintained for 2, 4 or 6 weeks on a white background and for the same periods on a black background. The peptides were resolved under dissociating conditions by gel exclusion chromatography on Sephadex G-50 and they were detected by radioimmunoassay with antibodies to β-endorphin, α,N-acetyl β-endorphin and α-MSH. The β-endorphin-related peptides separated into two fractions of different molecular size. Further purification of the peptides in each fraction was by ion exchange chromatography on SP-Sephadex C-25 and by high-pressure liquid chromatography. The α-MSH-related peptides were resolved by gel exclusion and ion exchange chromatography. The purified β-endorphin- and α-MSH-immunoreactive peptides were identified by comparison of their chromatographic properties with the corresponding peptides from porcine pituitary or by comparison with synthetic peptides. The major form of β-endorphin in the pars intermedia of the frog adapted to a white background was identified as α,N-acetyl β-endorphin (1–8); it was accompanied by a small quantity of acetylated peptides with molecular size similar to β-endorphin. In contrast, the pars intermedia of the frogs adapted to a black background contained approximately equal amounts of α,N-acetyl β-endorphin (1–8) and the larger forms of β-endorphin. The higher molecular weight forms were identified as the α,N-acetyl derivatives of β-endorphin (1–26), (1–27) and (1–31); however after 6 weeks of white adaptation the sole remaining peptide in this group was the 26-residue peptide. An additional β-endorphin immunoreactive peptide, provisionally identified as β-endorphin (10–26), was present in both black- and white-adapted animals; the amounts of this peptide increased during white adaptation. Major differences in the processing of α-MSH were also observed. In the frogs adapted to a black background des-acetyl α-MSH greatly predominated over the acetyl form whereas after 6- weeks adaptation to a white background the acetylated peptide proved to be the principal component. The results demonstrate that the proteolytic processing of β-endorphin and the acetylation of α-MSH in Xenopus laevis are influenced by background adaptation. The formation of β-endorphin (1–8) appears to reflect the action of an endopeptidase that acts at the single arginine residue present at position 9. This cleavage does not appear to take place in mammalian β-endorphins where position 9 is occupied by lysine. Journal of Endocrinology (1992) 135, 469–478
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Clark, David C., Linda J. Smith, and Lesley C. Chaplin. "The Effect of Dephosphorylation on the Conformation of Peptides from β-Casein." Collection of Czechoslovak Chemical Communications 57, no. 2 (1992): 425–28. http://dx.doi.org/10.1135/cccc19920425.
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Peptides β(1-28) and β(1-52) incorporating residues 1-28 and 1-52 of β-casein were prepared by proteolysis of the protein using plasmin and chymotrypsin respectively. Analysis of the circular dichroism spectra of the isolated peptides revealed that limited levels of α-helix were formed only by peptide β(1-52) and then only in the presence of >40% trifluoroethanol (TFE). Partial dephosphorylation of the peptides by treatment with alkaline phosphatase resulted in the formation of significant levels of α-helix in both peptides in the presence of TFE. However, no α-helix was detected in either peptide in the absence of TFE.
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Olsen, Christian A., Gitte Bonke, Line Vedel, Anne Adsersen, Matthias Witt, Henrik Franzyk, and Jerzy W. Jaroszewski. "α-Peptide/β-Peptoid Chimeras." Organic Letters 9, no. 8 (April 2007): 1549–52. http://dx.doi.org/10.1021/ol070316c.
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Yin, Hang, Hua Zhu, Gaston Vilaire, Wei Li, Rustem I. Litvinov, William F. DeGrado, and Joel S. Bennett. "Activation of Platelet α Iibβ 3 by Exogenous Peptides Corresponding to the Transmembrane Domains of α Iib and β 3." Blood 106, no. 11 (November 16, 2005): 384. http://dx.doi.org/10.1182/blood.v106.11.384.384.
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Abstract The platelet fibrinogen receptor α IIbβ 3 exists in an equilibrium between inactive and active conformations. In its inactive conformation, the transmembrane (TM) domains of α IIb and β 3 interact, but they separate when α IIbβ 3 assumes its active conformation. Peptides corresponding to the α IIb TM domain form homodimers in vitro and in bacterial membranes and the interface that mediates this interaction overlaps with the interface that mediates the heteromeric association of the α IIb TM domain with that of β 3. Because the homomeric association of α IIb TM domain is relatively strong, we expected that peptides spanning the α IIb TM domain might activate α IIbβ 3 by binding to the α IIb TM domain, thereby disrupting the α IIb/β 3 TM domain heterodimer. We synthesized a 26 residue peptide corresponding to the α IIb TM domain, flanked by pairs of lysine residues to increase its solubility in water, and assessed its ability to activate washed or gel-filtered platelets in an aggregometer. Addition of 3 μM peptide induced platelet aggregation after a short lag, but unlike aggregation stimulated by ADP, peptide-induced aggregation was not preceded by platelet shape change. Nonetheless, like ADP-induced aggregation, peptide-induced aggregation was inhibited by EDTA and the α IIbβ 3-specific monoclonal antibody A2A9. On the other hand, pre-incubating platelets with PGE1 or apyrase caused only a small decrease in the rate and extent of peptide-induced aggregation, suggesting that the peptide induced aggregation by binding directly to α IIbβ 3. A peptide corresponding the β 3 TM domain behaved in an identical manner, whereas an unrelated peptide, the model TM domain MS-1, had no effect. Similarly, there was little response to an α IIb TM peptide in which glycines 972 and 976, the first and last residues of a GxxxG motif, were changed to leucine. Confirming that the α IIb TM peptide binds to α IIbβ 3, we found that a FITC-labeled α IIb TM peptide co-eluted with purified α IIbβ 3 during size exclusion gel filtration. To determine whether the latter interaction involved the α IIb TM domain, we used the TOXCAT assay. In TOXCAT, the α IIb TM domain-mediated dimerization of a fusion protein containing the α IIb TM domain interposed between maltose binding protein and the ToxR’ transcriptional activation domain in the inner membrane of E. coli drives the activation of the chloramphenicol acetyl transferase (CAT) gene. We found that adding the α IIb TM peptide to the bacterial growth medium consistently decreased CAT synthesis, implying that its presence impaired α IIb-mediated fusion protein dimerization. These results provide evidence for the presence of an α IIb/β 3 TM domain heterodimer in unstimulated human platelets and suggest that the GxxxG motif in the α IIb TM domain is involved in its formation. Because the homomeric interaction of α IIb and β 3 TM domains is substantially stronger than their heteromeric interaction, our data are also consistent with the hypothesis that the TM peptides disrupt the heterodimer which functions to maintain α IIbβ 3 in an inactive state. Lastly, the data suggest that stabilizing the α IIb/β 3 TM heterodimer may represent a new approach for the development of novel anti-platelet agents.
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Berlicki, Łukasz, Ludwig Pilsl, Edit Wéber, István M. Mándity, Chiara Cabrele, Tamás A. Martinek, Ferenc Fülöp, and Oliver Reiser. "Unique α,β- and α,α,β,β-Peptide Foldamers Based on cis-β-Aminocyclopentanecarboxylic Acid." Angewandte Chemie International Edition 51, no. 9 (January 26, 2012): 2208–12. http://dx.doi.org/10.1002/anie.201107702.
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Jin, Yi, Janet Hammer, Michelle Pate, Yu Zhang, Fang Zhu, Erik Zmuda, and Jack Blazyk. "Antimicrobial Activities and Structures of Two Linear Cationic Peptide Families with Various Amphipathic β-Sheet and α-Helical Potentials." Antimicrobial Agents and Chemotherapy 49, no. 12 (December 2005): 4957–64. http://dx.doi.org/10.1128/aac.49.12.4957-4964.2005.
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ABSTRACT Many naturally occurring antimicrobial peptides comprise cationic linear sequences with the potential to adopt an amphipathic α-helical conformation. We designed a linear 18-residue peptide that adopted an amphipathic β-sheet structure when it was bound to lipids. In comparison to a 21-residue amphipathic α-helical peptide of equal charge and hydrophobicity, this peptide possessed more similar antimicrobial activity and greater selectivity in binding to and inducing leakage in vesicles composed of bacterial membrane lipids than vesicles composed of mammalian membrane lipids (J. Blazyk, R. Weigand, J. Klein, J. Hammer, R. M. Epand, R. F. Epand, W. L. Maloy, and U. P. Kari, J. Biol. Chem. 276:27899-27906, 2001). Here, we compare two systematically designed families of linear cationic peptides to evaluate the importance of amphipathicity for determination of antimicrobial activity. Each peptide contains six lysine residues and is amidated at the carboxyl terminus. The first family consists of five peptides with various capacities to form amphipathic β-sheet structures. The second family consists of six peptides with various potentials to form amphipathic α helices. Only those peptides that can form a highly amphipathic structure (either a β sheet or an α helix) possessed significant antimicrobial activities. Striking differences in the abilities to bind to and induce leakage in membranes and lipid vesicles were observed for the two families. Overall, the amphipathic β-sheet peptides are less lytic than their amphipathic α-helical counterparts, particularly toward membranes containing phosphatidylcholine, a lipid commonly found in mammalian plasma membranes. Thus, it appears that antimicrobial peptides that can form an amphipathic β-sheet conformation may offer a selective advantage in targeting bacterial cells.
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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.
Full textDissertations / Theses on the topic "Α/β Peptide"
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Das, Chittaranjan. "Designed β-Hairpin, β-Sheet And Mixed α-β Structures In Synthetic Peptides." Thesis, Indian Institute of Science, 2000. http://hdl.handle.net/2005/263.
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Synthetic construction of protein molecules has been widely pursued over the last two decades. A primary goal behind de novo protein design has been to build minimal systems by capturing the essential features of protein structures. Such minimal models can be used to understand underlying principles governing folding, structure, and function of proteins molecules. Several approaches envisioning successful construction of synthetic proteins have been described over the years, some of them being admirably successful (DeGrado et al, 1999; Richardson et al> 1992; Baltzer, 1998). Specific patterning of polar and apolar residues in synthetic sequences has been widely used to achieve designed polypeptide structures like helix bundles (DeGrado et ah, 1999) and (3-sheets (Smith and Regan, 1997; Lacroix et a/., 1998), with reliance on hydrophobic driving forces for folding. Our laboratory has been pursuing a distinctly alternative approach, that employs stereochemically constrained amino acids to generate specific secondary structures which can then be assembled into composite structures by appropriately chosen linking segments. This approach, which involves linking prefabricated modules of secondary structures can be termed as a "Meccano set" approach to protein design (Balaram, 1992). The studies embodied in the present thesis describe attempts at construction of synthetic polypeptide motifs using the stereochemically directing influence of conformationally constrained amino acid residues, such as DPro or Aib (α-aminoisobutyric acid). This thesis is subdivided into 8 chapters, with Chapter 1 providing a perspective of the field of protein design. Subsequent chapters (2-8) describe studies directed towards the specific goal of construction of polypeptide motifs.
Chapter 2 describes synthesis and conformational characterization of two octapeptides Boc-Leu-Val-Val-DPro-LAla-Leu-Val-Val-OMe (1) and Boc-Leu-Val-Val-DPro-DAla-Leu-Val-Val-OMe (2), designed to investigate the effect of specific β-turn stereochemistry on β-hairpin structures. 500 MHz NMR studies establish that both peptides 1 and 2 adopt predominantly β-hairpin conformations in chloroform and methanol solutions, with interstrand registry established by observation of long-range nuclear Overhauser effects (NOEs). Specific NOEs provide evidence for a type II' β-turn conformation for the DPro-LAla segment in 1, while the NMR data suggest that a type I' DPro-DAla β-turn conformation predominates in the peptide 2. The crystal structure of 1 reveals two independent molecules in the crystallographic asymmetric unit, both of which adopt β-hairpin conformations nucleated by a type II’ β-turn across DPro-LAla and stabilized by 3 cross strand hydrogen bonds. These designed β-hairpins with defined tight turns produce characteristic vibrational circular dichroism (VCD) patterns, demonstrating the utility of VCD as a probe for conformational analysis of β-hairpins.
In Chapter 3, we present conformational analysis on designed β-hairpin sequences incorporating a 'Phe-Phe' residue pair at a non-hydrogen bonding position. Two octapeptides Boc-Leu-Phe-Val-DPro-Gly-Leu-Phe-Val-OMe and Boc-Leu-Phe-Val-DPro-Ala-Leu-Phe-Val-OMe were synthesized and conformationally characterized by 500 MHz NMR spectroscopy. Specific NOEs observed in solution provide conclusive evidence favoring specific orientation effects pertaining to the 'Phe-Phe' pair. The peptides exhibited anomalous electronic CD, which has been explained in terms of aromatic contributions by the side chain chromophores. Interestingly, the VCD patterns obtained for these peptides were almost identical to those obtained for other β-hairpins, described in Chapter 2.
Chapter 4 describes the synthesis and conformational analysis of designed decapeptide sequences with centrally located DPro-Xxx β-trun segments. Two sequences Boc-Met-Leu»Phe-Val'DPro-Ala-Leu-Val-Val-Phe-OMe (1) and Boc-Met-Leu-Val-Val-^ro-Gly-Leu-Val-Val-Phe-OMe (2) were designed to study the effect of chain length elongation, of β-strands, on designed β-hairpin structures. 500 MHz NMR studies establish β-hairpin folds in both these sequences, with strand segments aligned even at the termini of the structures.
Multi-stranded, antiparallel β-sheet structures can be generated by successive placement of β-hairpin sequences in a single polypeptide chain. The successful construction of three stranded β-sheet structures is described in Chapter 5 of this dissertation. A 14-residue peptide Boc-Leu-Phe-Val-DPro-Gly-Leu-Val-Leu-Ala-DPro-Gly-Phe-Val-Leu-OMe (LFV14) was designed such that it is composed of three strand segments linked by two DPro-Gly turn segments. The peptide showed excellent solubility in apolar media, permitting detailed conformational analysis by 500 MHz NMR spectroscopy in organic solvents. Observation of long-range, interstrand NOEs, diagnostic of multiple hairpin structures, provides conclusive evidence for a predominantly populated three stranded β-sheet structure in solution. Extension of this strategy has been described in which an 18-residue peptide, Arg-Gly-Thr-Ile-Lys-DPro-Gly-Val-Thr-Phe-Ala-DPro-Ala-Thr-Lys-Tyr-Gly-Arg, was designed with enhanced solutility in water to probe (β-sheet structure formation in aqueous and mixed aqueous-methanol systems. NMR data provided conclusive evidence in favor of the desired structure being significantly populated in methanol and methanol-water mixtures (50 %, v/v). In water, spectroscopic evidence suggests that the long-range order expected of a three-stranded structure is lost, possibly due to water invading the interstrand hydrogen bonds.
Successful construction of a four-stranded antiparallel β-sheet structure has been
demonstrated in Chapter 6. A 26-residue peptide Arg-Gly-Thr-Ile-Lys»DPro-Gly-Ile-Thr-
Phe-Ala-DPro-Ala-Thr-Val-Leu-Phe-Ala-Val-DPro-Gly-Lys-Thr-Leu-Tyr-Arg was designed to have four strand segments linked by three DPro-Xxx turn segments. The peptide exhibited excellent NMR properties permitting structure determination by analysis of NOE data, which revealed that a four stranded β-sheet structure is indeed populated in methanol. Structural studies on this peptide in mixed methanol-water established that the four stranded β-sheet is appreciably populated at a composition of 50 % (v/v) methanol-water mixture, with the β-sheet structure still detectable even at a composition of 70 % water-30 % methanol. In a completely aqueous environment, the β-sheet structures is significantly disrupted, presumably due to solvent invasion. The nucleating β-turns, however, appear to have retained their structural integrity even in this competitive environment.
Chapter 7 describes the insertion of L-Lactic acid (Lac), a hydroxy acid, into polypeptide helices stabilized by a-aminoisobutyricacid (Aib). This study was undertaken to investigate the effect of hydrogen bond deletion on peptide helices. Crystal structure determination of three oligopeptides containing Lac residues has been performed. Peptide 1, Boc-Val-Ala-Leu-Aib-Val-Lac-Leu-Aib-Val-Ala-Leu-OMe, and peptide 2, Boc-Val-Ala-Leu-Aib-Val-Lac-Leu-Aib-Val-Leu-OMe adopt completely helical conformations in the crystalline state, with the Lac(6) residue comfortably accommodated in the center of a helix. NMR studies of peptide 1 and its all amide analog 4, Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-Aib-Val-Ala-Leu-OMe, provide firm evidence for a continuous helical segment in both the cases. In a 14-residue peptide 3, Boc-Val-Ala-Leu-Aib- Val- Ala-Leu- Val- Ala-Leu- Aib-Val-Lac-Leu-OMe, residues Val( 1 )-Leu( 10) adopt a helical conformation, which is terminated by formation of a Schellman motif, with Aib(ll) as the site of chiral reversal. The loss of the hydrogen bond at the C-terminus appears to facilitate the chiral reversal at Aib(l 1).
In the final section of this thesis, Chapter 8, successful construction of a synthetic motif containing two distinct elements of secondary structure, a (β-hairpin and a helix, has been described. The design of a 17-residue peptide Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-Gly-Gly-Leu-Phe-Val-DPro-Gly-Leu-Phe-Val-OMe, BH17, is based on a modular approach, in which previously characterized β-hairpin (Leu-Phe-Val-DPro-Gly-Leu-Phe-Val) and helix (Val-Ala-Leu-Aib-Val-Ala-Leu) modules are linked by a Gly-Gly linker. The positioning of the achiral Gly residue at position 8 facilitates termination of the potential helical segment (residues 1-7) by formation of a Schellman motif. Gly(9) is anticipated to be the sole conformationally flexible residue. NMR studies on BH17 indicated the presence of both the helix (residues 1-7) and the β-hairpin (residues 10-17) structures in the sequence, with four major conformational possibilities at the linking segment. Crystal structure determination of BH17 revealed that the two elements of structure are approximately arranged in an orthogonal fashion. The crystal structure validates the original premise that a modular assembly strategy may be viable for the construction of larger synthetic structures.
Chapter 9 summarises the major results of this thesis.
(For formulae, please refer "pdf" format)
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Kil, Hyun Joo. "Design & Synthesis of Peptidomimetics Adopting Secondary Structures for Inhibition of p53/MDM2 Protein-protein Interaction and Multiple Myeloma Cell Adhesion." Scholar Commons, 2014. https://scholarcommons.usf.edu/etd/5051.
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The protein-protein interactions (PPIs) occur when two or more proteins are bound together. Also, this protein-protein interactions (PPIs) cause the various biological processes in the body. Due to this reason, abilities of controlling or inhibiting PPIs can give us promising advantages like (1) better understanding of biological systems, (2) development of new diagnostic approaches for health or disease, and (3) establishment of novel molecular therapeutics. Many proteins adopt the secondary structures, where most of protein-protein interactions take place. -Helices and -sheets are the prevalent secondary conformations, but there are extended secondary structures such as -hairpins, -turns, 310 helix, and so on. As a result, construction of molecules mimicking these protein secondary structures is tractable target for drug design.
Moreover, in drug discovery, designing peptidomimetics or non-peptidic mimetics is a popular strategy instead using peptides or truncated peptides because peptides or truncated peptides are prone to proteolysis and degraded in the body. Also, peptidomimetics and non-peptidic mimetics have not only the similar topology as peptides but also resistance to proteolysis. Due to these advantages, in this study, peptidomimetics or non-peptidic mimetics were synthesized and tested for different targets: (1) synthesis of non-peptidic -helical mimetics for p53-MDM2 inhibition, (2) solution-phase synthesis of -hairpin peptide for the inhibition of multiple myeloma cells (MM) adhesion, and (3) synthesis of -hairpin peptoid-peptide hybrids.
The synthesis in all three different studies was succeeded, but they still need some improvements. For instance, non-peptidic -helical mimetics, terpyrimidyl derivatives, were synthesized successfully, but they did not show any bioactivity against p53-MDM2. Also, they have a solubility problem. Based on these results, it is necessary to improve the pharmacokinetic properties and bioactivity by changing the substituents on the rings or structures.
The -hairpin peptide for the second case already showed good bioactivity against multiple myeloma (MM). For the next level of bio-study, the considerable amount of a -hairpin peptide was demanded. In order to make the substantial -hairpin peptide, the solution phase peptide synthesis was chosen instead of the solid phase peptide synthesis because of the cost-effect. Two methodology were tried for the solution-phase peptide synthesis: (1) segment ligation and (2) continuous synthesis. In the former case, the -hairpin peptide synthesis was successful, but, in the latter case, it is necessary to investigate the appropriate coupling reagents for each step.
Peptoid-peptide hybrids has been one of the popular peptidomimetics in the last two decades. Also, mimicking the peptide secondary structure in peptoids has been studied extensively these days. The combination of these two factors was the goal for the third case. Because peptoid-peptide hybrids with a secondary structure can be recognizable by native proteins and resistant to proteolysis. So far, three sets of peptoid-peptide hybrids were synthesize and checked the secondary structure formation by using NMR. However, there was no indication of the secondary structure formation in the three sets of peptoid-peptide hybrids. This result suggests that it is necessary to introduce the more constrained components in peptoid-peptide hybrids.
In the above three chapters, it has been tried to find the new drug candidates by synthesizing peptidomimetics or non-peptidic mimetics. Even though the synthesis was successful, some intended results such as the bioactivity or the secondary structure formation were not obtained. However, these results can give us the inspirations to improve properties of peptidomimetics or non-peptidic mimetics for a certain purpose, which leads to earn the intended results and eventually find new drug candidates.
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Lopez-Perez, Elvira. "La voie α-sécrétase de maturation de la protéine précurseur du peptide β-amyloi͏̈de dans la maladie d'Alzheimer : activités protéolytiques et régulation." Nice, 2000. http://www.theses.fr/2000NICE5459.
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La maladie d'Alzheimer est un syndrome neurodégénératif caractérisé par la présence de plaques séniles et de dégénérescences neurofibrillaires. Le constituant majeur des plaques séniles est le peptide β-amyloi͏̈de (Aβ) qui est issu de la maturation protéolytique de la protéine précurseur du peptide β-amyloi͏̈de ( βAPP). Deux activités enzymatiques, les β- et γ- sécrétases libèrent respectivement les extrémités N- et C-terminales du peptide Aβ. La βAPP peut subir une maturation protéolytique alternative dans la séquence du peptide Aβ par une α-sécrétase, prévenant ainsi la production du peptide amyloi͏̈de. De plus, le clivage α-sécrétase génère un fragment soluble (APPα) qui est neurotrophique et citoprotecteur. La maturation de la βAPP est sous le contôle de voies de phosphorylation, comme la voie régulée par la protéine kinase C (PKC). (. . . )
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Saraiva, rosa Nathalie. "Synthèse diastéréosélective de molécules azotées α-trifluorométhylées - Élaboration et études conformationnelles de petits peptides incorporant des acides β-aminés trifluorométhylés." Thesis, Reims, 2017. http://www.theses.fr/2017REIMS013.
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Les N-tert-butanesulfinamides, des auxiliaires chiraux développés par Ellman il y a une vingtaine d’années, sont à l’heure actuelle de plus en plus sollicités pour la préparation d’amines chirales fonctionnalisées, et ce, du fait de la disponibilité des deux énantiomères à faible coût et de leurs conditions de déprotection faciles à mettre en œuvre. Cependant, leur utilisation dans le cadre de la synthèse de dérivés trifluorométhylés quaternaires à partir des N-tert-butanesulfinylalkyl- ou arylcétimines correspondantes, connues pour leur faible hydrostabilité, reste à ce jour très limitée. Les éthers d’hémiaminals trifluorométhylés dérivés de l’auxiliaire d’Ellman constituent des analogues stables de ces cétimines. Ils permettent de générer in situ la cétimine correspondante, qui peut subir l’addition de l’espèce nucléophile présente. Ce manuscrit relate les différentes réactions étudiées sur ces éthers d’hémiaminals, donnant ainsi accès à des synthons azotés α-trifluorométhylés quaternaires de façon énantiopure : d’une part, les amines homoallyliques obtenues par l’addition d’allylalanes, qui, après quelques étapes, permettent de fournir les azétidines trifluorométhylées correspondantes, et d’autre part, les β3,3-aminoacides trifluorométhylés, préparés via une réaction de Reformatsky hautement diastéréosélective. Les acides β-aminés ainsi préparés ont été réinvestis dans des couplages peptidiques en solution pour la préparation d’une gamme d’α/β- et de β-di- et tripeptides, sur lesquels des études conformationnelles préliminaires ont été menées à l’état solide et/ou en solution.Mots-clés : Auxiliaire d’Ellman, Addition nucléophile, Couplage peptidique en solution, Dérivé azoté α-trifluorométhylé, Éther d’hémiaminal, Synthèse asymétriqueChiral N-tert-butansulfinamides, developped by Ellman 20 years ago, have been increasingly applied for the preparation of chiral functionnalized amines, because of the affordability of both enantiomers and of their mild conditions of cleavage. However, the use of theses auxiliaries for the synthesis of quaternary trifluoromethyl derivatives remains quite limited, the corresponding trifluoromethyl ketoimines being highly unstable.Chiral N-tert-butanesulfinyl alkyl(aryl) trifluoromethyl hemiaminal ethers have been developped to be used as bench-stable surrogates of these ketoimines : once under reaction conditions, they afford the corresponding ketoimine in situ, which can be subject to a nucleophilic addition.In this manuscript, different reactions led on these hemiaminal ethers are described, affording valuable and optically pure trifluoromethylated quaternary building-blocks : on the one hand, homoallylic amines, obtained by the addition of allylalane species, and which can afford, after a few steps, teh corresponding trifluoromethyl azetidines, and on the other hand, chiral trifluoromethyl β3,3-amino acids, afforded by a highly diastereoselective Reformatsky reaction.These β 3,3-amino acids have been then involved in solution-phase peptide couplings in order to synthetise a wide range of α/β- and β-di- and tripeptides, whose conformation have been the object of preliminary studies in the solid state and/or in solution.Key-words : Ellman auxiliary, Nucleophilic addition, Solution-phase peptide coupling, α-trifluoromethylated nitrogen derivative, Hemiaminal ether, asymmetric synthesis
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Attal, Sandra. "Utilisation des enzymes en chimie organique : application à la synthèse d'esters de dipeptides par la papai͏̈ne et de galactosyl-sérines par les α-et β-galactosidases." Paris 5, 1992. http://www.theses.fr/1992PA05P614.
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Collet, Magalie. "Peptidonucléoside polyoxine J, inhibiteur de la chitine synthase : approches vers la synthèse du nucléoside C2' - désoxy -C2' fluoré, et synthèse de l'acide 5-O-carbamoyle polyoxamique." Toulouse 3, 2004. http://www.theses.fr/2004TOU30198.
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Les polyoxines, peptidonucléosides d'origine naturelle connus pour leurs propriétés antifongiques en tant qu'inhibiteurs de la biosynthèse de la chitine, sont des composés très actifs in vitro, mais présentant une faible biodisponibilité in vivo. Le but de cette thèse a donc été de trouver des méthodes de synthèse d'analogues C2'-désoxy-C2'-fluorés de la thymine polyoxine C, constituant nucléosidique de la polyoxine J (la plus active), ainsi que d'obtenir, d'une manière originale, la partie peptidique non naturelle de la polyoxine J, à savoir l'acide 5-O-carbamoyle polyoxamique. Après une présentation de la cible biologique et de l'intérêt de l'introduction d'un atome de fluor, ce travail s'est divisé en deux grandes parties. Tout d'abord, deux approches de la synthèse de la partie nucléosidique fluorée par passage par des 2-désoxy-2-fluorobutyrolactones, puis une optimisation de la synthèse de la partie peptidique via la formation d'un intermédiaire oxazolidinonePolyoxins, which form an important class of peptidyl nucleosidic antibiotics that selectively and competitively inhibit chitin synthase, are very active components in vitro, but weakly bioavailable in vivo. The subject of this thesis has been to found new synthetic methods to access to C2'-fluoro-C2'-deoxy analogues of thymine polyoxine C, nucleosidic part of polyoxine J (the more active one), and to obtain, by an original way, the non natural peptidic moiety of polyoxine J, which is the 5-O-carbamoyl polyoxamic acid. After a presentation of the biological target and the interest of the introduction of a fluorine atom, this work is divided into two parts. Fisrt, two approaches of the fluorinated nucleosodic part using 2-deoxy-2-fluorobutyrolactones as intermediates, and then, an optimization of the synthesis of the peptidic part using the formation of an oxazolidonone intermediate
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Norgren, Anna S. "Conformational Stability!? : Synthesis and Conformational Studies of Unnatural Backbone Modified Peptides." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7420.
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Patino, Nadia. "Peptides fluorés : intérêt et synthèse de peptides incorporant dans leur structure un acide α-aminé β-fluoré." Nice, 1989. http://www.theses.fr/1989NICE4274.
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Willems, Hendrika Maria Gerarda. "The design and synthesis of non-peptidic α-helix and β-turn mimetics." Thesis, University of Cambridge, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.627463.
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Claudel, Stéphanie. "Les peptides Vinylogues : des nouveaux outils pour la préparation d'analogues contraints de la substance P, de γ-aminoacides α, β-hydroxylés et de dihydroxylactames." Nancy 1, 2004. http://www.theses.fr/2004NAN10039.
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Le travail présenté concerne la conception et la synthèse de peptides modifiés et se divise en deux parties. La première est l'introduction d'un résidu aminé vinylogue à stéréochimie cis et trans dans un undécapeptide, la substance P pour comprendre ses interactions avec le récepteur NK-1. Une seconde étude a été orientée vers l'obtention de g-aminopeptides par hydrogénation des acides aminés vinylogues précédents. Cette modification structurale a donné un nouvel analogue de la SP. La seconde partie est de la méthodologie de synthèse en utilisant les peptides vinylogues. Un premier chapitre, la dihydroxylation de ces motifs avec une induction asymétrique en utilisant des réactifs chiraux, permet l'obtention de g-aminoacides dihydroxylés. Un second chapitre, une application par la synthèse totale d'un produit naturel issu d'une plante nyctinastique. Et le dernier chapitre est une autre application, la synthèse de lactames dihydroxylés conduisant à la synthèse de nouveaux azasucresThis work concerns conception and synthesis of modified peptides and is divided in two parts. Firstly, it's the insertion of vinylogous amino acids with cis and trans conformation in neuropeptide of eleven amino acids which is substance P in order to understand its interaction with NK-1 receptor. A second study has been oriented on the preparation of g-amino peptides by hydrogenation of previous vinylogous amino acids. This structural modification has given a new SP's analog which has been tested. The second part is the methodology of synthesis using vinylogous peptides and is divided in three chapters. First one presents dihydroxylation's results of these residues with an asymmetric induction using chiral catalyst to obtain dihydroxylated g-amino acids. Second one is an application of these studies with a total synthesis of natural product extracted from nyctinastic plant. And the last one deals with preparation of dihydroxylated lactams leading to the synthesis of new azasugars
Book chapters on the topic "Α/β Peptide"
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Hartsock, Wendy J., and Robert S. Hodges. "Rational Design of Amphipathic α-Helical and Cyclic β-Sheet Antimicrobial Peptides: Specificity and Therapeutic Potential." In Peptide Drug Discovery and Development, 91–117. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA, 2011. http://dx.doi.org/10.1002/9783527636730.ch4.
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Singh, T. P., B. Padmanabhan, P. Narula, A. K. Saxena, C. Betzel, P. Sharma, and S. Dey. "Design of Specific Peptide Structures and Subtilisin Enzyme Inhibitors Using α, β-Dehydro-Residues." In Advances in Experimental Medicine and Biology, 11–20. Boston, MA: Springer US, 1996. http://dx.doi.org/10.1007/978-1-4613-0319-0_3.
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Blaskovich, M. A., and G. A. Lajoie. "Stereoselective synthesis of β-substituted-β-hydroxy α-amino acids and β,γ-unsaturated α-amino acids from serine and threonine." In Peptides, 167–69. Dordrecht: Springer Netherlands, 1994. http://dx.doi.org/10.1007/978-94-011-0683-2_52.
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Boitel, Brigitte, Myriam Ermonval, Ulrich Blank, and Oreste Acuto. "T-Cell Antigen and MHC Recognition: Molecular Analysis of Human α/β TCR Specific for a Tetanus Toxin-Derived Peptide." In T Lymphocytes, 1–16. Boston, MA: Springer US, 1992. http://dx.doi.org/10.1007/978-1-4615-3054-1_1.
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Long, Yi-cheng, Fei-ning Ye, Yun-hua Ye, and Qi-yi Xing. "Studies on the interconversions of the neuroexcitotoxin β-N-oxalo-L-α, β-diaminopropionic acid from Panax species and its isomer α-N-oxalo-L-α, β-diaminopropionic acid." In Peptides, 189–90. Dordrecht: Springer Netherlands, 1993. http://dx.doi.org/10.1007/978-94-010-9066-7_55.
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Blaskovich, M. A., A. W. Wong, and G. A. Lajoie. "Synthesis of optically enriched β,γ-unsaturated α-amino acids." In Peptides 1994, 205–6. Dordrecht: Springer Netherlands, 1995. http://dx.doi.org/10.1007/978-94-011-1468-4_85.
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Tung, Roger D., Chong-Qing Sun, Don Deyo, and Daniel H. Rich. "Asymmetric syntheses of β-OH and β-OH, γ-alkyl α-amino acids: Analogs of the unusual cyclosporin amino acid MeBmt." In Peptides, 149–51. Dordrecht: Springer Netherlands, 1988. http://dx.doi.org/10.1007/978-94-010-9595-2_43.
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Diaz-Diaz, M., S. Mzengeza, O. P. Ward, J. F. Honek, and G. Lajoie. "Asymmetric synthesis of β-hydroxy L-α-amino acids using aldolase from Pseudomonas sp." In Peptides, 517–18. Dordrecht: Springer Netherlands, 1992. http://dx.doi.org/10.1007/978-94-011-2264-1_198.
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Viso, Alma, and Roberto Fernández de la Pradilla. "Synthetic Approaches to α,β-Diamino Acids." In Amino Acids, Peptides and Proteins in Organic Chemistry, 411–40. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA, 2010. http://dx.doi.org/10.1002/9783527631766.ch9.
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Ibuka, T., K. Nakai, H. Habashita, Y. Hotta, A. Otaka, N. Fujii, N. Mimura, Y. Miwa, T. Taga, and Y. Yamamoto. "A new route to stereochemically pure (E)-alkene dipeptide isosteres from β-aziridino-α,β-enoates via organocopper reaction." In Peptides 1994, 674–75. Dordrecht: Springer Netherlands, 1995. http://dx.doi.org/10.1007/978-94-011-1468-4_309.
Full textConference papers on the topic "Α/β Peptide"
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Lasota, Anika, Oliwia Fraczak, Adriana Muchowska, Aleksandra Misicka, Michal Nowakowski, Maciej Maciejczyk, Andrzej Ejchart, and Aleksandra Olma. "Structure-Activity Relationships of Constrained Dermorphin Analogues Containing an α-Alkyl-β-Substituted Alanines." In The 24th American Peptide Symposium. Prompt Scientific Publishing, 2015. http://dx.doi.org/10.17952/24aps.2015.073.
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Bezeaud, A., and M. C. Guillin. "FUNCTIONAL CHARACTERIZATION OF HUMAN β-THROMBIN." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644665.
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Autolysis or tryptic hydrolysis converts β-thrombin (α-T) t β-thrombin ( β -T), and subsequently β-T to y-thrombin (γ-T). Human β-T differs from native α-T by the loss of a unique ll-re-sidues peptide arising from the B chain. Unlike its bovine counterpart, human β-Tisa transient intermediate and its enzymatic properties had not yet been investigated using purified materiaL After 3 min incubation of human β-T with trypsin-sepharose, the resulting β-T was separated from α- and γ-T by chromatography on Biorex 70 with a gradient from 10 mM to 500 mM phosphate at pH 8. No major differences were found between human α- and β-T regarding the kinetic parameters (Km, kcat, kcat/Km) on S 2238, nor the rate of inactivation by TLCK. In contrast, inhibition of β-T by DFP was slower (k = 426 ±[; 10.8 M-1 min−1) compared to α-T (764.5 ± 19.5 M−11min−1and the inhibition constant for benzami-dine was higher with β-T (Ki = 11.2 ± x00B1;.2 10−4 M) compared to α-T (Ki = 2.86± 0,06 10−4 M). The drastic reduction in the clotting activity of β-T (25 u mg−1 versus 3000 u mg−1 for α-T) was further explored by measuring the affinity of β-T for fibrinogen and fibrin. Human fibrinogen was used as a competitor in the inactivation of thrombin by DFP : 10 μM fibrinogen prevented the inhibition of α-T by DFP but failed to modify the inactivation rate of α-T. Binding of thrombin to fibrin was studied using fibrin monomers covalently linked to sepharose 4B, equilibrated in 50mM Tris, pH 7.5, 50 mM NaCl : β -T did not bind to the resin, whereas α-T was retained and eluted upon application of a NaCl gradient.In conclusion, the loss of the peptide extending from lie (63) to Arg (73) in the thrombin B chain is responsiblefor multiple defects in thrombin enzymatic activity. Although, the three active site residues Ser (205), His (43), Asp (99) remain in an active configuration, subtle changes are induced in the microenvironment of the catalytic Ser (205), and in particular, in the primary binding pocket. In addition, the results presented in this study indicate thatthe loss of clotting activity is mainly the result of a decreased affinity for fibrinogen and fibrin, suggesting that the structural changesaffect both the fibrinopeptide groove and the anionic binding site involved in fibrinogen/fibrin recognition.
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Bacon-Baguley, Theresa, Suzanne Kendra-Franczak, and Daniel Walz. "THROMBOSPONDIN SPECIFICALLY INTERACTS WITH AMINO ACID SEQUENCES WITHIN THE A α- AND B β- CHAINS OF FIBRINOGEN." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643822.
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Thrombospondin (TSP) is responsible for the secretion-dependent phase of platelet aggregation. The mechanism of this action is believed to be through the binding of TSP to fibrinogen, resulting in the stabilization of the platelet aggregate. It has been established that the binding of fibrinogen to the platelet surface is dependent upon peptide sequences present, respectively, in the Aa- and y-chains. We have hypothesized that the binding of TSP to fibrinogen is also dependent upon unique fibrinogen peptide sequences. To test this hypothesis we have examined the interaction of TSP and f.ih.r.inogen. using..a.-blat-b.inding assaLy of reduced fibrinogen, the separated fibrinogen chains, selected fibrinogen domains or peptides generated from cyanogen bromide cleaved chains. Iodinated TSP bound specifically to the Aα - and Bβ - chains. Binding to these chains was calcium independent, mutually exclusive and could be blocked either by preincubation of TSP with 9.4 μ M fibrinogen or by preincubation of fibrinogen with 1.1 nM thrombospondin. TSP bound to the D and DD plasmin fragment of fibrinogen; TSP interacted exclusively with the B-chain component of the DD fragment. The cyanogen bromide fragments of the separated Aα - and Bβ -chains were resolved through a combination of gel filtration and reverse-phase chromatography. TSP was found to bind to a single peptide within these fibrinogen chains. These studies demonstrate that thrombospondin interacts with at least two distinct sites on fibrinogen, and these sites differ from those already described for fibrinogen binding to platelets.
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Dejana, E., F. Breviario, F. Bussolino, L. Mussoni, and A. Mantovani. "PLEIOTROPIC EFFECT OF INTERLEUKIN-1 ON ENDOTHELIAL CELLS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643984.
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Inflammatory processes are often associated with pathological alteration of the vessel wall and sometimes with local or disseminated thrombotic phenomena. Interleukin-1 (IL-1), a monokine produced by activated cells of the monocyte/macrophage lineage and responsible of most of the changes associated with the inflammatory acute phase response, appears to dramatically' modify several endothelial cell (EC) functions. Some groups including ours (for review 1) have shown that IL-1 stimulates prostacyclin (PGI2), platelet activating factor (PAF), plasminogen activator inhibitor (PAi), thromboplastin (PCA) synthesis by cultured human EC in vitro. In addition IL-1 can act directly on EC to increase neuthophil and other leukocyte adhesion on their surface (2). All these effects, in contrast to previously described inducers, require a long time of interaction (30 min to 4 hours) of IL-1 with EC to be apparent and then last for several hours (4 to 12 hours). The IL-1 effects are concentration dependent (minimal active concentration being about 1 unit/ml) and require protein and RNA synthesis. To better define the structural requirement for IL-1 induced modification of EC functions we compared the activity of different IL-1 molecular species. Our approach is based on the observation that IL-1 is indeed a family of polypeptides biochemically different(3). At least two dissimilar gene products have been cloned with very limited homology (denominated α and β). These molecules, though biochemically different, share common activities and possibly the same receptor in different cell types. On EC we investigated whether the αand β IL-1 forms have similar biological activities (4). All the IL-1 preparations used were active on thymocyte costimulatory assay and comparison was made on the basis of the concentrations of these agents equally active on this assay.Human recombinant IL- αandβ (hr IL-1 α and hr IL-1 β) were both active in stimulating PGI2, PCA, PAi production and in increasing neutrophil adhesion to EC. In contrast PAF synthesis was Stimulated by hr IL-1 α but not by hr IL-1 β. Murine recombinant IL-1 (mr IL-1 α highly homologous with hr IL-1 < α, at concentrations able to maximally activate thymocytes was inactive on PGI2, PCA and in increasing neutrophil adhesion to EC. In contrast, mr IL-1 α was equally effective on PAF production as hr IL-1 α. A short peptide fragment of hr IL-1β (fragment 167-171) was synthesized on the basis of its predicted exposure on the surface of the molecule (5). This peptide is also located in a region (150-186) of high homology between hr IL-1α and β sequences. While the peptide showed high thymocyte activation capacity it was inactive on EC activities. Overall these results indicate that the α and β forms of human IL-1 elicit largely but not completely overlapping patterns of response in EC. In addition they suggest that the structural requirement for activation by IL-1 is not identical for thymocytes and EC. These results might provide some clues to novel strategies for modulation of IL-1 vascular and immunological activities.1. Mantovani A. and E. Dejana (1987) Biochem. Pharm. 36:301.2. Bevilacqua M. et al. (1985) J. Clin. Invest. 76:20033. Dinarello C.A. (1985) J. Clin. Immunol. 5:287.4. Dejana E. et al. (1987) Blood 69:695.5. Antoni G. et al. (1987) J. Immunol, (in press).
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Berndt, M. C., X. Du, L. Beutler, W. J. Booth, and P. A. Castaldi. "LOCALIZATION OF FUNCTIONAL DOMAINS ON HUMAN PLATELET GP Ib-IX COMPLEX BY EPITOPE ANALYSIS WITH MONOCLONAL ANTIBODIES." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1642923.
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There is now considerable evidence that glycoprotein (GP) Ib plays an important functional role in the von Willebrand factor (vWF)-dependent adhesion of platelets to exposed vascular subendothelium and in the a-thrombin activation of platelets, and that GP IX is important for quinine/quinidine drug-dependent antibody platelet recognition. GP Ib (Mr = 170 KD) consists of two disulfide-linked subunits, Iba (Mr = 135 KD) and Ibβ (Mr = 25 KD), and exists as a heterodimer complex with GP IX (Mr = 22 KD). In this study we have used a panel of 10 antiGP Ib-IX complex monoclonal antibodies to define the functional domains on this complex. Immunoprecipitation of trypsin-treated GP Ib-IX complex revealed that the monoclonal antibodies mapped into three distinct groups: FMC 25, AK 1 and SZ 1, epitopes on the membrane-associated fragment (GP IX and an ≃25 KD remnant of the α-chain disulfide linked to the β-chain); AK 3 and WM 23, epitopes on the central macroglycopeptide core (90 KD); AN 51, SZ 2, AK 2, AP 1 and HIP 1, epitopes on peptide tail (45 KD). Crossblocking studies indicated that with the exception of AK 1 and SZ 1, the monoclonal antibodies were directed against distinct epitopes. All five monoclonal antibodies directed against the peptide tail region blocked ristocetin-dependent vWF-platelet interaction whereas the other five monoclonal antibodies were without effect, indicating that the 45 KD peptide tail region at the plasma end of the α-chain of GP Ib contained the vWF binding domain. Similarly, only the three monoclonal antibodies directed against the membrane-associated region interfered with drug-dependent antibody-platelet interaction.By western blot analysis, α-thrombin bound to the 45 KD peptide tail region. However, only AP 1 interfered significantly with the α-thrombin-dependent aggregation of platelets. This panel of epitope-defined monoclonal antibodies should be of value in further defining the structure-function relationships of this important membrane complex.
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Blodgett, Karl, Timothy Zwier, and Patrick Walsh. "SINGLE-CONFORMATION IR AND UV SPECTROSCOPY OF A PROTOTYPICAL HETEROGENEOUS α/β-PEPTIDE: IS IT A MIXED-HELIX FORMER?" In 71st International Symposium on Molecular Spectroscopy. Urbana, Illinois: University of Illinois at Urbana-Champaign, 2016. http://dx.doi.org/10.15278/isms.2016.mi12.
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Kwon, Sunkuk, Shi Ke, Jessica P. Houston, Wei Wang, Qingping Wu, Chun Li, and Eva M. Sevick Muraca. "In vivo pharmacokinetic analysis for fluorescently labeled RGD peptide targeted to the α v β 3 integrin in Kaposi"s sarcoma." In Biomedical Optics 2005, edited by David Kessel. SPIE, 2005. http://dx.doi.org/10.1117/12.589399.
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Hantgan, R. R. "LOCALIZATION OF THE DOMAINS OF FIBRIN INVOLVED IN BINDING TO PLATELETS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643773.
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The molecular basis of platelet-fibrin interactions has been investigated by using synthetic peptides as potential inhibitors of binding fibrin protofibrils and fibrinogen to ADP-stimulated platelets, adhesion of fibrin fibers to the platelet surface, and platelet-mediated clot retraction. Synthetic peptides RGDS and HHLGGAKQAGDV, corresponding to regions of the fibrinogen α and γ chains previously identified as platelet recognition sites, inhibited the binding of radiolabelled soluble fibrin oligomers to ADP-stimulated platelets with IC50 values of 12 and 40 μM, respectively. The IC50 values obtained with fibrinogen as the ligand were 3-fold higher. Synthetic GPRP and GHRP, corresponding to the N-terminal sequences of the fibrin α and β chains, were minimally effective in blocking soluble fibrin oligomer binding to ADP-stimulated platelets. The extent of fibrin:platelet adhesion was determined with a microfluorimetric technique which measures the quantity of fluorescein-labelled fibrin attached to the surface of platelets. The signal obtained from the brightly fluorescent platelet:fibrin adducts was time- and concentration-dependent, and was fully inhibited by a monoclonal antibody directed against the glycoprotein II:IIIa complex (HP1-1D, kindly provided by Dr. W. Nichols). Inhibition of fibrin:platelet adhesion by RGDS, HHGGAKQAGDV, and GHRP all exhibited a similar, linear dependence on the peptide concentration, reaching 1/2 maximum at about 200 μM, suggesting nonspecific effects. GPRP inhibited fibrin assembly but did not appear to have specific effects on fibrin:platelet adhesion. The time course of clot retraction was followed by right angle light scattering intensity measurements. Only RGDS affected clot retraction, causing a 4-fold decrease in rate at 230 μM. These results indicate that fibrinogen and fibrin protofibrils, which are obligatory intermediates in the fibrin assembly pathway, share a set of common platelet recognition sites located at specific regions of the α and γ chains of the multinodular fibrin(ogen) molecules. The RGDS site is also involved in mediating interactions between the three dimensional fibrin network and ADP-stimulated platelets.
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Valensin, Daniela, Henryk Kozlowski, Isabella Tessari, Simone Dell'Acqua, Luigi Bubacco, Luigi Casella, Elena Gaggelli, and Gianni Valensin. "Interactions of metal ions with α synuclein and amyloid β peptides." In INTERNATIONAL CONFERENCE OF COMPUTATIONAL METHODS IN SCIENCES AND ENGINEERING 2014 (ICCMSE 2014). AIP Publishing LLC, 2014. http://dx.doi.org/10.1063/1.4897691.
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Han, Zhihao, Shuaishuai Gong, Zhiyu Qian, and Yueqing Gu. "Virtual screened peptides with high affinity to integrin α 5 β 1 for precise tumor identification and treatment." In Biophotonics and Immune Responses XV, edited by Wei R. Chen. SPIE, 2020. http://dx.doi.org/10.1117/12.2544502.
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