Готові списки джерел за темами / Β-strand

Добірка наукової літератури з теми "Β-strand"

Автор: Grafiati

Опубліковано: 10 грудня 2022

Оновлено: 28 січня 2023

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Статті в журналах з теми "Β-strand"

Zhang, Ning, Shan Gao, Lei Zhang, Jishou Ruan та Tao Zhang. "Statistical Analysis of Terminal Extensions of Protein β-Strand Pairs". Advances in Bioinformatics 2013 (28 січня 2013): 1–7. http://dx.doi.org/10.1155/2013/909436.

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The long-range interactions, required to the accurate predictions of tertiary structures of β-sheet-containing proteins, are still difficult to simulate. To remedy this problem and to facilitate β-sheet structure predictions, many efforts have been made by computational methods. However, known efforts on β-sheets mainly focus on interresidue contacts or amino acid partners. In this study, to go one step further, we studied β-sheets on the strand level, in which a statistical analysis was made on the terminal extensions of paired β-strands. In most cases, the two paired β-strands have different lengths, and terminal extensions exist. The terminal extensions are the extended part of the paired strands besides the common paired part. However, we found that the best pairing required a terminal alignment, and β-strands tend to pair to make bigger common parts. As a result, 96.97% of β-strand pairs have a ratio of 25% of the paired common part to the whole length. Also 94.26% and 95.98% of β-strand pairs have a ratio of 40% of the paired common part to the length of the two β-strands, respectively. Interstrand register predictions by searching interacting β-strands from several alternative offsets should comply with this rule to reduce the computational searching space to improve the performances of algorithms.

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KEDARISETTI, KANAKA DURGA, MARCIN J. MIZIANTY, SCOTT DICK, and LUKASZ KURGAN. "IMPROVED SEQUENCE-BASED PREDICTION OF STRAND RESIDUES." Journal of Bioinformatics and Computational Biology 09, no. 01 (February 2011): 67–89. http://dx.doi.org/10.1142/s0219720011005355.

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Accurate identification of strand residues aids prediction and analysis of numerous structural and functional aspects of proteins. We propose a sequence-based predictor, BETArPRED, which improves prediction of strand residues and β-strand segments. BETArPRED uses a novel design that accepts strand residues predicted by SSpro and predicts the remaining positions utilizing a logistic regression classifier with nine custom-designed features. These are derived from the primary sequence, the secondary structure (SS) predicted by SSpro, PSIPRED and SPINE, and residue depth as predicted by RDpred. Our features utilize certain local (window-based) patterns in the predicted SS and combine information about the predicted SS and residue depth. BETArPRED is evaluated on 432 sequences that share low identity with the training chains, and on the CASP8 dataset. We compare BETArPRED with seven modern SS predictors, and the top-performing automated structure predictor in CASP8, the ZHANG-server. BETArPRED provides statistically significant improvements over each of the SS predictors; it improves prediction of strand residues and β-strands, and it finds β-strands that were missed by the other methods. When compared with the ZHANG-server, we improve predictions of strand segments and predict more actual strand residues, while the other predictor achieves higher rate of correct strand residue predictions when under-predicting them.

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Terwilliger, Thomas C. "Rapid model building of β-sheets in electron-density maps". Acta Crystallographica Section D Biological Crystallography 66, № 3 (12 лютого 2010): 276–84. http://dx.doi.org/10.1107/s0907444910000302.

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A method for rapidly building β-sheets into electron-density maps is presented. β-Strands are identified as tubes of high density adjacent to and nearly parallel to other tubes of density. The alignment and direction of each strand are identified from the pattern of high density corresponding to carbonyl and Cβatoms along the strand averaged over all repeats present in the strand. The β-strands obtained are then assembled into a single atomic model of the β-sheet regions. The method was tested on a set of 42 experimental electron-density maps at resolutions ranging from 1.5 to 3.8 Å. The β-sheet regions were nearly completely built in all but two cases, the exceptions being one structure at 2.5 Å resolution in which a third of the residues in β-sheets were built and a structure at 3.8 Å in which under 10% were built. The overall average r.m.s.d. of main-chain atoms in the residues built using this method compared with refined models of the structures was 1.5 Å.

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Vischer, Henry F., Joke C. M. Granneman, and Jan Bogerd. "Opposite Contribution of Two Ligand-Selective Determinants in the N-Terminal Hormone-Binding Exodomain of Human Gonadotropin Receptors." Molecular Endocrinology 17, no. 10 (October 1, 2003): 1972–81. http://dx.doi.org/10.1210/me.2003-0172.

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Abstract The nine leucine-rich repeat-containing exodomains of the human FSH receptor (hFSH-R) and the human LH/chorionic gonadotropin receptor (hLH-R) harbor molecular determinants that allow the mutually exclusive binding of human FSH (hFSH) and human LH (hLH)/human chorionic gonadotropin (hCG) when these hormones are present in physiological concentrations. Previously, we have shown that the β-strands of hLH-R leucine-rich repeats 3 and 6 can confer full hCG/hLH responsiveness and binding when simultaneously introduced into a hFSH-R background without affecting the receptor’s responsiveness to hFSH. In the present study, we have determined the nature of contribution of each of these two β-strands in conferring hCG/hLH responsiveness to this mutant hFSH-R. Human LH-R β-strand 3 appeared to function as a positive hCG/hLH determinant by increasing the hCG/hLH responsiveness of the hFSH-R. In contrast, mutagenesis of hFSH-R β-strand 6, rather than the introduction of its corresponding hLH-R β-strand, appeared to allow the interaction of hCG/hLH with the hFSH-R. Hence, hFSH-R β-strand 6 functions as a negative determinant and, as such, restrains binding of hCG/hLH to the hFSH-R. Detailed mutagenic analysis revealed that the ability of the hFSH-R to interact with hCG/hLH depends primarily on the identity of two amino acids (Asn104, a positive LH-R determinant, and Lys179 a negative FSH-R determinant) that are situated on the C-terminal ends of β-strands 3 and 6, respectively.

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Gao, Yang, Yanxiang Cui, Tara Fox, Shiqiang Lin, Huaibin Wang, Natalia de Val, Z. Hong Zhou, and Wei Yang. "Structures and operating principles of the replisome." Science 363, no. 6429 (January 24, 2019): eaav7003. http://dx.doi.org/10.1126/science.aav7003.

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Visualization in atomic detail of the replisome that performs concerted leading– and lagging–DNA strand synthesis at a replication fork has not been reported. Using bacteriophage T7 as a model system, we determined cryo–electron microscopy structures up to 3.2-angstroms resolution of helicase translocating along DNA and of helicase-polymerase-primase complexes engaging in synthesis of both DNA strands. Each domain of the spiral-shaped hexameric helicase translocates sequentially hand-over-hand along a single-stranded DNA coil, akin to the way AAA+ ATPases (adenosine triphosphatases) unfold peptides. Two lagging-strand polymerases are attached to the primase, ready for Okazaki fragment synthesis in tandem. A β hairpin from the leading-strand polymerase separates two parental DNA strands into a T-shaped fork, thus enabling the closely coupled helicase to advance perpendicular to the downstream DNA duplex. These structures reveal the molecular organization and operating principles of a replisome.

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Haworth, Naomi L., та Merridee A. Wouters. "Between-strand disulfides: forbidden disulfides linking adjacent β-strands". RSC Advances 3, № 46 (2013): 24680. http://dx.doi.org/10.1039/c3ra42486c.

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HAWORTH, NAOMI L., LINA L. FENG, and MERRIDEE A. WOUTERS. "HIGH TORSIONAL ENERGY DISULFIDES: RELATIONSHIP BETWEEN CROSS-STRAND DISULFIDES AND RIGHT-HANDED STAPLES." Journal of Bioinformatics and Computational Biology 04, no. 01 (February 2006): 155–68. http://dx.doi.org/10.1142/s0219720006001734.

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Redox-active disulfides are capable of being oxidized and reduced under physiological conditions. The enzymatic role of redox-active disulfides in thiol-disulfide reductases is well-known, but redox-active disulfides are also present in non-enzymatic protein structures where they may act as switches of protein function. Here, we examine disulfides linking adjacent β-strands (cross-strand disulfides), which have been reported to be redox-active. Our previous work has established that these cross-strand disulfides have high torsional energies, a quantity likely to be related to the ease with which the disulfide is reduced. We examine the relationship between conformations of disulfides and their location in protein secondary structures. By identifying the overlap between cross-strand disulfides and various conformations, we wish to address whether the high torsional energy of a cross-strand disulfide is sufficient to confer redox activity or whether other factors, such as the presence of the cross-strand disulfide in a strained β-sheet, are required.

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Vischer, Henry F., Joke C. M. Granneman та Jan Bogerd. "Identification of Follicle-Stimulating Hormone-Selective β-Strands in the N-Terminal Hormone-Binding Exodomain of Human Gonadotropin Receptors". Molecular Endocrinology 20, № 8 (1 серпня 2006): 1880–93. http://dx.doi.org/10.1210/me.2005-0202.

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Abstract Glycoprotein hormone receptors contain large N-terminal extracellular domains (ECDs) that distinguish these receptors from most other G protein-coupled receptors. Each glycoprotein hormone receptor ECD consists of a curved leucine-rich repeat domain flanked by N- and C-terminal cysteine-rich regions. Selectivity of the different glycoprotein hormone receptors for their cognate hormones is exclusively determined by their ECDs and, in particular, their leucine-rich repeat domain. To identify human (h)FSH-selective determinants we used a gain-of-function mutagenesis strategy in which β-strands of the hLH receptor (hLH-R) were substituted with their hFSH receptor (hFSH-R) counterparts. Introduction of hFSH-R β-strand 1 into hLH-R conferred responsiveness to hFSH, whereas hLH-R mutants harboring one of the other hFSH-R β-strands displayed none or very limited sensitivity to hFSH. However, combined substitution of hFSH-R β-strand 1 and some of the other hFSH-R β-strands further increased the sensitivity of the mutant hLH-R to hFSH. The apparent contribution of multiple hFSH-R β-strands in providing a selective hormone binding interface corresponds well with their position in relation to hFSH as recently determined in the crystal structure of hFSH in complex with part of the hFSH-R ECD.

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Chandrasekhar, Srivari, Ambadi Sudhakar, Marelli Udaya Kiran, Bathini Nagendra Babu та Bharatam Jagadeesh. "β-Strand mimetics: formation of bend-strands in oligomers of enantiomeric β-amino acids". Tetrahedron Letters 49, № 52 (грудень 2008): 7368–71. http://dx.doi.org/10.1016/j.tetlet.2008.10.031.

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Tsai, James H., Amy Sue Waldman та James S. Nowick. "Two New β-strand Mimics". Bioorganic & Medicinal Chemistry 7, № 1 (січень 1999): 29–38. http://dx.doi.org/10.1016/s0968-0896(98)00225-9.

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Більше джерел

Дисертації з теми "Β-strand"

Chen, Hongyuan. "Development of macrocyclic β-strand calpain cysteine protease inhibitors". Thesis, University of Canterbury. Chemistry, 2011. http://hdl.handle.net/10092/5582.

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The work in this thesis reports studies directed to developing a calpain cysteine protease inhibitor that could be of value in slowing cataract development in humans. The work focuses on the development of macrocyclic compounds which can have advantages over acyclic compounds due to their resistance to proteolytic hydrolysis, improved selectivity, bioavailability and membrane permeability. A review of X-ray crystal structures of natural and synthetic calpain inhibitors complexed with the cysteine protease calpain show the inhibitors generally bind in the enzyme active site in an extended β-strand conformation. The calpain inhibitor SJA-6017 has been identified as a suitable lead compound. The importance of the para-fluoro group in SJA-6017 has been investigated. Modifications have been made to constrain this basic structure within a macrocycle and restrict the peptide chain as a β-strand conformation. Macrocycle CAT811 is a potent calpain 1 and 2 inhibitor and shows promise in slowing the progression of cortical cataract in trials with sheep having a hereditary propensity towards the development of cataract. In this thesis I report studies directed to improve the yield of the key RCM macrocyclisation step in the synthesis of aldehyde CAT811 and of three ester analogues (2.1, 2.3 and 2.4). I also report the development of a more commercial route to CAT811 not involving RCM but using intramolecular nucleophilic cyclisation. This intramolecular nucleophilic cyclisation strategy was attempted for the preparation of a histidine containing macrocyclic ester (4.1a) but was unsuccessful. An alternate strategy involving intramolecular lactamization proved successful for the synthesis of histidine-based macrocyclic esters (4.1a-4.3a). Reduction to the corresponding alcohols (4.1b-4.3b) was successful and oxidation of (4.1b and 4.3b) afforded the corresponding aldehydes (4.1c and 4.3c) for biological assay against ovine calpain 2. Aldehyde 4.3c has an IC50 of 1 μM and the corresponding alcohol 4.3b shows no activity (IC50 > 50 μM) consistent with the modelling which indicated that these two compounds did not adopt a β-strand conformation in the docking studies. Aldehyde 4.1c, on the other hand, shows significant inhibitory activity with an IC50 of 238 nM but as expected the corresponding alcohol 4.1b shows little activity (IC50 = 29 μM). Modelling studies showed that both the aldehyde 4.1c and the alcohol 4.1b on docking can form a β-strand with appropriate H-bonding interactions. The aldehyde is more active than the alcohol due to the reactivity of the aldehyde warhead allowing for the reversible formation of a hemiacetal. A similar difference in reactivity is observed for CAT811 (30 nM) and its alcohol analogue (700 nM). These results demonstrate the value of molecular modelling as a screening mechanism before unproductive synthetic work is considered.

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Aitken, Steven Geoffrey. "Design, synthesis and testing of β-strand mimics as protease inhibitors". Thesis, University of Canterbury. Chemistry, 2006. http://hdl.handle.net/10092/1984.

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Chapter 1 gives background information on proteases and discusses the concept of protease inhibition as a therapeutic strategy for humans. It introduces the key concept that conformation defines biological activity. It also outlines how proteases almost universally bind their substrate/inhibitors in an extended β-strand conformation. The use of calpain as a prototype protease for the testing of β-strand mimics synthesised later in the thesis is also discussed. Chapter 2 describes how molecular modeling was used to rationalise the structure based activity relationships (SAR) of known calpain inhibitors. Molecular modeling was then used to successfully design a number of acyclic β-strand mimics. The synthesis and testing of eight such inhibitors is described. The most potent β-strand mimic prepared was 2.13. This was determined to have an IC₅₀ of 30 nM against calpain II. Chapter 3 outlines the history and application of ring closing metathesis (RCM) to the synthesis of cyclic compounds. The attempted synthesis of an eight membered cyclic nitrogen to nitrogen conformationally constrained dipeptide is described. The synthesis of a conformationally constrained β-amino acid calpain inhibitor (3.73) is also described. A novel calpain inhibitor motif was designed in Chapter 4. On the basis of this an in-silico combinatorial library of two hundred and eighty eight possible β-strand templates was prepared. Conformational analysis of this library was performed and from this a number of excellent β-strand templates were identified and selected for synthesis. The preparation of ten β-strand templates is described. New microwave irradiation methodology was developed to achieve this. vii The formation of a six-membered catalyst deactivating chelate is also proposed to explain why some dienes fail to undergo RCM. Two methods to circumvent the formation of such a chelate are outlined. The addition of Lewis acid chloro-dicyclohexyl borane to the RCM reaction mixture and chain length alteration are investigated. Chapter 5 describes the design of macrocyclic β-strand mimics using induced fit molecular modelling. The physicochemical properties of these were calculated in-silico. From this analysis a number of Tyr-XX-Gly based and Tyr-XX-Cys based macrocyclic calpain inhibitors were selected for synthesis. The preparation and testing of these are described. In the Tyr-XX-Gly macrocyclic system a number of variables were investigated and numerous SAR implications concluded. Aldehyde 5.14 was identified as the best electrophilic warhead macrocyclic calpain inhibitor with an IC₅₀ against calpain II of 27 nM. The best non-electrophilic warhead macrocycle (5.13) had an IC₅₀ against calpain II of 704 nM. Chapter 6 describes synthetic optimisation for the preparation of calpain inhibitors 2.13, 5.14 and 5.17. Multi-gram quantities of each were prepared. Aldehydes 2.13 and 5.14 were evaluated as anti-cataract agents using in-vivo cataract sheep model. Both of these β-strand mimics were demonstrated to retard cataract development. Macrocycle 5.14 was found to be the most effective, decreasing the rate of cataract development between forty four and forty nine per cent relative to control. Chapter 7 outlines the attempted development of RCM methodology for the chiral synthesis of α-α disubstituted amino acid lactams. In addition, methodology for the stereoselective incorporation of a C-N constrained β-amino acid carbocycle into a peptide or peptidomimetic is described.

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Lutz, Henrik [Verfasser], Bodo [Akademischer Betreuer] Laube та Gerhard [Akademischer Betreuer] Thiel. "Identification and impact of Topoisomerase II β induced DNA double-strand breaks in Glioblastoma multiforme: NMDA-receptor signaling pathway as target structure / Henrik Lutz ; Bodo Laube, Gerhard Thiel". Darmstadt : Universitäts- und Landesbibliothek Darmstadt, 2019. http://d-nb.info/1193177863/34.

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Ganai, Rais Ahmad. "Structural and biochemical basis for the high fidelity and processivity of DNA polymerase ε". Doctoral thesis, Umeå universitet, Institutionen för medicinsk kemi och biofysik, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-97689.

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DNA polymerase epsilon (Pol ε) is a multi-subunit B-family DNA polymerase that is involved in leading strand DNA replication in eukaryotes. DNA Pol ε in yeast consists of four subunits, Pol2, Dpb2, Dpb3, and Dpb4. Pol2 is the catalytic subunit and Dpb2, Dpb3, and Dpb4 are the accessory subunits. Pol2 can be further divided into an N-terminal catalytic core (Pol2core) containing both the polymerase and exonuclease active sites and a C-terminus domain. We determined the X-ray crystal structure of Pol2core at 2.2 Å bound to DNA and with an incoming dATP. Pol ε has typical fingers, palm, thumb, exonuclease, and N-terminal domains in common with all other B-family DNA polymerases. However, we also identified a seemingly novel domain we named the P-domain that only appears to be present in Pol ε. This domain partially encircles the nascent duplex DNA as it leaves the active site and contributes to the high intrinsic processivity of Pol ε. To ask if the crystal structure of Pol2core can serve as a model for catalysis by Pol ε, we investigated how the C-terminus of Pol2 and the accessory subunits of Pol ε influence the enzymatic mechanism by which Pol ε builds new DNA efficiently and with high fidelity. Pre-steady state kinetics revealed that the exonuclease and polymerization rates were comparable between Pol2core and Pol ε. However, a global fit of the data over five nucleotide-incorporation events revealed that Pol ε is slightly more processive than Pol2 core. The largest differences were observed when measuring the time for loading the polymerase onto a 3' primer-terminus and the subsequent incorporation of one nucleotide. We found that Pol ε needed less than a second to incorporate the first nucleotide, but it took several seconds for Pol2core to incorporate similar amounts of the first nucleotide. B-family polymerases have evolved an extended β-hairpin loop that is important for switching the primer terminus between the polymerase and exonuclease active sites. The high-resolution structure of Pol2core revealed that Pol ε does not possess an extended β-hairpin loop. Here, we show that Pol ε can processively transfer a mismatched 3' primer-terminus between the polymerase and exonuclease active sites despite the absence of a β-hairpin loop. Additionally we have characterized a series of amino acid substitutions in Pol ε that lead to altered partitioning of the 3'primer-terminus between the two active sites. In a final set of experiments, we investigated the ability of Pol ε to displace the downstream double-stranded DNA while carrying out DNA synthesis. Pol ε displaced only one base pair when encountering double-stranded DNA after filling a gap or a nick. However, exonuclease deficient Pol ε carries out robust strand displacement synthesis and can reach the end of the templates tested here. Similarly, an abasic site or a ribonucleotide on the 5'-end of the downstream primer was efficiently displaced but still only by one nucleotide. However, a flap on the 5'-end of the blocking primer resembling a D-loop inhibited Pol ε before it could reach the double-stranded junction. Our results are in agreement with the possible involvement of Pol ε in short-patch base excision repair and ribonucleotide excision repair but not in D-loop extension or long-patch base excision repair.

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Blomberg, David. "Synthesis of β-turn and pyridine based peptidomimetics". Doctoral thesis, Umeå universitet, Kemi, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1104.

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Despite the unfavorable pharmacokinetic properties associated with peptides, they are still of great interest in drug development due to a multitude of interesting biological functions. The development of peptidomimetics strives to maintain or improve the biological activity of a peptide concurrently with removing the unwanted properties. This thesis describes two synthetic approaches to peptidomimetics with particular emphasis on secondary structure mimetics. First the design, synthesis and evaluation of two beta-turn mimetics incorporated in the endorphin Leu-enkephalin is presented. The beta-turn mimetics were stabilized by replacement of the intramolecular hydrogen bond with an ethylene bridge, and the amide bond between Tyr and Gly was replaced with an ether linkage. Linear analogues of the two mimetics were also synthesized. The peptidomimetics and their linear analogues were evaluated in a competitive binding assay at two opiate receptors, my and delta. One of the cyclized beta-turn mimetics was found to be a delta receptor antagonist with an IC50 value of 160 nM. Second a synthetic strategy to a beta-strand mimetic using 2-fluoro-4-iodopyridine as scaffold is described. The synthesis involved a Grignard exchange reaction on the pyridine scaffold using an amino acid derivative as electrophile followed by an SNAr reaction using an amine as nucleophile. The synthesis of a tripeptidomimetic of Leu-Gly-Gly and attempts to introduce chiral building blocks at the C-terminal, as well as studies towards elongated mimetics are presented. Two additional studies deal with the synthesis of two classes of potential thrombin inhibitors based on the pyridine scaffold. The first class contain pyridine as central fragment (P2 residue) substituted with a para-amidinobenzylamine group as P1 residue and various benzoyl groups as P3 residues. Three potential thrombin inhibitors were synthesized and found to be microM inhibitors in an enzymatic assay. In the second class, the pyridine ring serves as P3 residue. This class also lacks a strongly basic group in the P1 position. A small library of eight compounds were synthesized and evaluated in the enzymatic assay. Unfortunately, these compounds lacked inhibitory activity.

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Bose, Anindita. "Modulation of glycogen synthase kinase 3β (GSK3 β) activation and tau phosphorylation by double stranded RNA dependent protein kinase (PKR]". Paris 7, 2010. http://www.theses.fr/2010PA077049.

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La kinase PKR (double stranded RNA dépendent protein kinase) est une kinase pro-apoptotique qui contrôle la traduction des protéines. Des études antérieures ont montré que la kinase PKR était activée dans les neurones en dégénérescence au cours de la maladie d'Alzheimer (MA). La kinase GSK3 bêta participe à la phosphophorylation de la protéine tau qui compose les « neurofibrillary tangles » au cours de la MA. PKR peut activer indirectement GSK 3 bêta dans les cultures de cellules. Nous montrons dans ce travail que PKR, est colocalisée avec GSK 3 bêta et tau phosphorylée dans les neurones des cerveaux de patients MA. Dans les cultures ed celules neurales SH-SY5Y , le stress du réticulum endoplasmique induit par la tunicamycin ou la neurotoxicité du peptide A bêta 1-42, active PKR, induit ractivation de GSK3, produit la phosphorylation de tau et conduit à l'apoptose. Les inhibiteurs pharmacologiques de PKR ou les si RNA de PKR atténuent les effets induits par ces stress dans les cultures de cellules. PKR pourrait représenter une nouvelle cible thérapeutique capable de diminuer la mise en jeu de processus pathologiques au cours de la MA conduisant à la dégénérescence neuronale
PKR or double-stranded RNA dependent kinase is a pro-apoptotic kinase that controls protein translation. Previous studies revealed that activated PKR is increased in AD brains. Glycogen Synthase Kinase Aβ(CS K3β) is responsible for tau phosphorylation and PKR can indirectly activate GSK3β in cell cultures. The goal of this work was to détermine if PKR could simultaneously trigger GSK3J5 activation and tau phosphorylation and apoptosis. In AD brains, both activated kinases co-localized with phosphorylated tau in neurons. In SH-SY5Y cell cultures, tunicamycin and Api_42 activate PKR, GSK3β and induce tau phosphorylation which are both attenuated by PKR inhibitors or PKR siRNA. Our results demonstrate that PKR is able to modulate GSK3β activation, tau phosphorylation and apoptosis in neuroblastoma cells exposed to tunicamycin or Aβ PKR could represent a potent pharmacological target to attenuate neurodegeneration and tau phosphorylation

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Gholami, Sara [Verfasser]. "Association of neighboring β-Strands to form the β-barrel structure of the voltage-dependent anion channel, human isoform 1 (hVDAC1) precedes membrane insertion and is largely driven by polar interactions between basic and acidic amino acid side-chains / Sara Gholami". Kassel : Universitätsbibliothek Kassel, 2020. http://d-nb.info/1232431893/34.

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Pehere, Ashok D. "New peptide-based templates constrained into a β-strand by Huisgen cycloaddition". Thesis, 2012. http://hdl.handle.net/2440/87372.

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Chapter One introduces the concept of peptide 'secondary structure' with an emphasis on β-strand geometry in macrocycles. This structural design is crucial for targeting different proteases. The significance of the macrocylic β-strand ‘bioactive’ conformation is discussed in detail. In particular the exploitation of the conformationally constrained peptidomimetic macrocylic backbone, which is constrained by a number of synthetic approaches to lock the ‘bioactive’ conformation in place. Chapter Two describes simple and scalable methodology for the preparation of N-Cbz protected amino acids by reaction with Cbz-Cl which uses a mixture of aqueous sodium carbonate and sodium bicarbonate to maintain the appropriate pH. This method proceeds without the formation of by-products. The method is extended to large scale preparation of an intermediate zofenopril, an ACE inhibitor. Chapter Three describes new peptidic templates constrained into a β-strand geometry by linking acetylene and azide containing P₁ and P₃ residues of a tripeptide by Huisgen cycloaddition. The conformations of the macrocycles are defined by NMR studies and those that best define a β-strand are shown to be potent inhibitors of the protease calpain. The β-strand templates presented and defined here are prepared under optimized conditions and should be suitable for targeting a range of proteases and other applications requiring such geometry. Chapter four describes a new approach to non-covalent peptide-based nanotubular or rodlike structures, whereby the monomeric units are preorganised into a β-strand geometry that templates the formation of an extended and unusual parallel β-sheet rod-like structure. The conformational constraint is introduced by Huisgen cycloaddition to give a triazolebased macrocycle, with the resulting self-assembled structures stabilized by a well-defined series of intermolecular hydrogen bonds. Chapter Five the 26S proteasome has emerged over the past decade as an attractive therapeutic target in the treatment of cancers. Here, we report new tripeptide aldehydes that are highly specific for the chymotrypsin-like catalytic activity of the proteasome. These new CT-L specific proteasome inhibitors demonstrated high potency and specificity for cancer cells, with therapeutic windows superior to those observed for benchmark proteasome inhibitors, MG132 and Bortezomib. Constraining the peptide backbone into the β-strand geometry was associated with decreased activity in vitro and reduced anticancer activity, suggesting that the proteasome prefers to bind a conformationally flexible ligand. Using these new proteasome inhibitors, we show that the presence of an intact p53 pathway significantly enhances cytotoxic activity, thus suggesting that this tumor suppressor is a critical downstream mediator of cell death following proteasomal inhibition. Chapter Six peptide derived protease inhibitors represent an important class of compounds with the potential to treat a wide range of serious medical conditions. Herein we describe the synthesis of a series of triazole containing macrocylic protease inhibitors preorganised in a β-strand conformation and evaluate their selectivity and potency against a panel of protease inhibitors. A series of acyclic azido-alkyne-based aldehydes is also evaluated for comparison. The macrocyclic peptidomimetics showed considerable activity towards Calpain II, Cathepsin L and S and the 26S proteasome chymotrypsin-like activity. Importantly, the first examples of potent and selective inhibitors of Cathepsin S were identified and shown to adopt a well-defined β-strand geometry by NMR, X-ray and molecular docking studies. Chapter Seven describes simple and efficient methodology for the selective acylation and alkylation of biotin at its 3′-nitrogen. This methodology is used to prepare of other biotin derivatives.
Thesis (Ph.D.) -- University of Adelaide, School of Chemistry and Physics, 2012

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Jones, Seth Adam. "β-strand mimicry as the basis for a universal approach to protease inhibition". Thesis, 2011. http://hdl.handle.net/2440/72156.

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This thesis describes the design, preparation, and testing of a range of protease inhibitors. Chapter One introduces the concept of peptidomimetics, and discusses how proteases almost universally bind their ligands in a β-strand conformation. The idea of constraining a compound into a biologically active conformation by the introduction of a ring or bridge is discussed. The technique of ring closing metathesis as a strategy for macrocyclisation is introduced. The chapter also discusses calpain and HIV proteases and their structures and implications in human disease. Chapter Two surveys the acyclic calpain inhibitors reported in the literature. A series of N-heterocyclic peptidic calpain inhibitors were docked in silico into an ovine m-calpain homology model using Glide, which revealed that compounds 2.60 – 2.67 all adopted a β-strand conformation upon binding. The modelling revealed low energy conformations of 2.60, 2.61 and 2.66 not in a β-strand geometry. The synthesis and testing of these inhibitors is described, with 2.63 displaying an IC₅₀ of 40 nM against m-calpain in an in vitro assay. Chapter Three describes the design and synthesis of the β-strand mimic macrocycle 3.8, which was prepared using ring closing metathesis. The chapter also describes the design of a number of calpain and HIV protease inhibitors that incorporate 3.8. Each inhibitor is designed to bind and inhibit a specific protease target. Chapter Four describes the synthesis and testing of a series of macrocyclic calpain and proteasome 20S inhibitors. The preparation of the aldehydes 3.9 and 3.10 by elaboration of the macrocycle 3.8 is described. As well, the preparation of 3.10 from the N-capped 4-fluorosulphonyl diene 4.4 is described. The most potent macrocycle in the series was 3.10, which displays an IC₅₀ against m-calpain of 2000 nM, and an IC₅₀ against the chymotrypsin like activity of proteasome 20S of 2 nM. Chapter Five describes the synthesis of a series of building blocks, and their use in the attempted preparation of the potential HIV protease inhibitor 3.12a, as well as the successful preparation of the potential HIV protease inhibitors 3.11 and 3.12b. Preliminary studies testing the biological activity of compounds 3.11, 3.12b and 5.21 found that they displayed a percentage inhibition of HIV-1 subtype B protease of 86, 63, and 26%, respectively. The Ki of 3.11 against HIV-1 subtype B protease was also determined to be 62 nM. The activity of 3.11 against HIV-1 protease establishes that the common macrocyclic core 3.8 can be incorporated into inhibitors of both calpain, and HIV-1 protease. Chapter Six describes the preparation of a key macrocycle by cross-metathesis. The preparation of 6.4 by cross-metathesis of the olefins 6.5 and 6.24 is described, as well as the elaboration of 6.4 to give the macrocycle 6.1. A systematic study of the cross-metathesis of the olefins 6.5, 6.6, 6.23 and 6.24 is described. Their percentage conversion to 6.4 was calculated using high performance liquid chromatography analysis. The highest conversion to 6.4 was found to be 60%, from the cross metathesis of an equimolar mixture of 6.6 and 6.23. Chapter Seven describes a multi-gram synthesis of the potent macrocyclic calpain inhibitor CAT0811. The key step in the synthesis is the base induced macrocyclisation of the iodopeptide 7.10 to give 7.6. The macrocycle 7.6 was also prepared by macrolactamisation of the pseudopeptide 7.9. The synthesis was found to be scalable, affordable and efficient, and removes the need for Grubbs’ 2nd generation catalyst (II).
Thesis (Ph.D.) -- University of Adelaide, School of Chemistry and Physics, 2011

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Lord, Rianne M., A. J. Hebden, C. M. Pask, I. R. Henderson, Simon J. Allison, S. L. Shepherd, Roger M. Phillips та P. C. McGowan. "Hypoxia-Sensitive Metal β‑Ketoiminato Complexes Showing Induced Single-Strand DNA Breaks and Cancer Cell Death by Apoptosis". 2015. http://hdl.handle.net/10454/9491.

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yes
A series of ruthenium and iridium complexes have been synthesized and characterized with 20 novel crystal structures discussed. The library of β-ketoiminato complexes has been shown to be active against MCF-7 (human breast carcinoma), HT-29 (human colon carcinoma), A2780 (human ovarian carcinoma), and A2780cis (cisplatin-resistant human ovarian carcinoma) cell lines, with selected complexes’ being more than three times as active as cisplatin against the A2780cis cell line. Selected complexes were also tested against the noncancerous ARPE-19 (retinal pigment epithelial cells) cell line, in order to evaluate the complexes selectivity for cancer cells. Complexes have also been shown to be highly active under hypoxic conditions, with the activities of some complexes increasing with a decrease in O2 concentration. The enzyme thioredoxin reductase is overexpressed in cancer cells, and complexes reported herein have the advantage of inhibiting this enzyme, with IC50 values measured in the nanomolar range. The anticancer activity of these complexes was further investigated to determine whether activity is due to effects on cellular growth or cell survival. The complexes were found to induce significant levels of cancer cell death by apoptosis with levels induced correlating closely with activity in chemosensitivity studies. As a possible cause of cell death, the ability of the complexes to induce damage to cellular DNA was also assessed. The complexes failed to induce double-strand DNA breaks or DNA cross-linking but induced significant levels of single-strand DNA breaks, indicating a mechanism of action different from that of cisplatin.
Lord RM, Hebden AJ, Pask CM, Henderson IR, Allison SJ, Shepherd SL, Phillips RM, McGowan PC

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Книги з теми "Β-strand"

Herwig, Sascha. β-Strang-Ausbildung eines Faltungsintermediates von BamA. Wiesbaden: Springer Fachmedien Wiesbaden, 2020. http://dx.doi.org/10.1007/978-3-658-29029-0.

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Herwig, Sascha. β-Strang-Ausbildung eines Faltungsintermediates von BamA: Adsorption an Lipidmembranen induziert lokale Sekundärstruktur in β-Strang 9. Springer Spektrum, 2020.

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Частини книг з теми "Β-strand"

Loughlin, Wendy A., and David P. Fairlie. "Recent Advances in β-Strand Mimetics." In Amino Acids, Peptides and Proteins in Organic Chemistry, 129–47. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA, 2011. http://dx.doi.org/10.1002/9783527631827.ch3.

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Del Valle, Juan R. "Heterocyclic Extended Peptide Surrogates for β-Strand Stabilization." In Topics in Heterocyclic Chemistry, 25–49. Cham: Springer International Publishing, 2015. http://dx.doi.org/10.1007/7081_2015_163.

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Pehere, Ashok D., and Andrew D. Abell. "Macrocyclic Protease Inhibitors Constrained into a β-Strand Geometry." In Proteases in Health and Disease, 181–92. New York, NY: Springer New York, 2013. http://dx.doi.org/10.1007/978-1-4614-9233-7_11.

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Choi, Yoonjoo. "Computational Identification and Design of Complementary β-Strand Sequences." In Methods in Molecular Biology, 83–94. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-1855-4_4.

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Bionda, Nina, and Rudi Fasan. "Peptidomimetics of α-Helical and β-Strand Protein Binding Epitopes." In Small Molecule Medicinal Chemistry, 431–64. Hoboken, NJ: John Wiley & Sons, Inc, 2015. http://dx.doi.org/10.1002/9781118771723.ch15.

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Huggins, Kelly N., and Niels H. Andersen. "Quantitating Amino Acid β-Strand Preferences, Turn Propensities and Cross-Strand Interactions in a Designed Hairpin Peptide." In Advances in Experimental Medicine and Biology, 71–72. New York, NY: Springer New York, 2009. http://dx.doi.org/10.1007/978-0-387-73657-0_31.

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Urban, Jan, Hiroshi Nakanishi, Cyprian O. Ogbu, Geoffrey Kozu, Kenneth Farber, Polina Kazavchinskaya, and Min S. Lee. "Bicyclic β-Strand Templates: Epimerization and Biological Activity of Non-Electrophilic Serine Protease Inhibitors." In Peptides: The Wave of the Future, 634–35. Dordrecht: Springer Netherlands, 2001. http://dx.doi.org/10.1007/978-94-010-0464-0_295.

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Herwig, Sascha. "Einleitung". У β-Strang-Ausbildung eines Faltungsintermediates von BamA, 1–18. Wiesbaden: Springer Fachmedien Wiesbaden, 2020. http://dx.doi.org/10.1007/978-3-658-29029-0_1.

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Herwig, Sascha. "Material und Methoden". У β-Strang-Ausbildung eines Faltungsintermediates von BamA, 19–28. Wiesbaden: Springer Fachmedien Wiesbaden, 2020. http://dx.doi.org/10.1007/978-3-658-29029-0_2.

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Herwig, Sascha. "Ergebnisse". У β-Strang-Ausbildung eines Faltungsintermediates von BamA, 29–43. Wiesbaden: Springer Fachmedien Wiesbaden, 2020. http://dx.doi.org/10.1007/978-3-658-29029-0_3.

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Тези доповідей конференцій з теми "Β-strand"

Seo, Yuji, Keita Yoshizaki, Keisuke Tamari, Yutaka Takahashi, Keisuke Otani, Masahiko Koizumi та Kazuhiko Ogawa. "Abstract 5205: Poly(ADP-ribose) polymerase inhibitors induce β-radiosensitization through an altered selection of DNA double-strand break repair pathways". У Proceedings: AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1538-7445.am2017-5205.

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Hwang, Wonmuk, and Matthew J. Lang. "Mechanism of Force Generation in Kinesin Motility." In ASME 2007 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2007. http://dx.doi.org/10.1115/sbc2007-175543.

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Conventional kinesin is a dimeric motor protein that uses adenosine triphosphate (ATP) to walk processively along the microtubule. Although its nucleotide dependent conformational switching and binding of the neck linker (NL) on the motor head are known to be key events in kinesin motility, the basic mechanism by which it amplifies a small conformational change upon ATP binding to generate the force of the walking stroke has not been known. We combined structural analysis with a set of molecular dynamics simulations to identify the 9-residue long N-terminal region, which we named the ‘cover strand’ (CS), as an additional element essential for kinesin’s power stroke. It operates by differentially forming a β-sheet with NL when ATP binds, whereby the ‘cover-neck bundle’ (CNB) has an inherent conformational bias that drives NL into its binding pocket on the motor head. After the initial stroke, the later half of NL, starting with the ‘asparagine latch’ in the middle, forms specific bonds with the motor head to ensure tight binding. We constructed the force map generated by CNB, which showed a forward bias in agreement with single molecule motility measurements. Our result is consistent with other experimental observations, including the estimated stall force and the transverse anisotropy. The novel mechanism of force generation by the dynamic folding of CNB appears to hold in various kinesin families, and elucidates the economy in the design principle of the smallest known processive motor.

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REVA, BORIS, та SID TOPIOL. "RECOGNITION OF PROTEIN STRUCTURE: DETERMINING THE RELATIVE ENERGETIC CONTRIBUTIONS OF β-STRANDS, α-HELICES AND LOOPS". У Proceedings of the Pacific Symposium. WORLD SCIENTIFIC, 1999. http://dx.doi.org/10.1142/9789814447331_0016.

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