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排序方式: 共有914条查询结果,搜索用时 15 毫秒
911.
Kevin H. Mayo Judith Haseman Elena Ilyina Beulah Gray 《Biochimica et Biophysica Acta (BBA)/General Subjects》1998,1425(1):81-92
Novel peptide 33mers have been designed by incorporating β-conformation stabilizing residues from the β-sheet domains of α-chemokines and functionally important residues from the β-sheet domain of human neutrophil bactericidal protein (B/PI). B/PI is known for its ability to kill bacteria and to neutralize the action of bacterial endotoxin (lipopolysaccharide, LPS) which can induce septic shock leading to eventual death. Here, the goal was to make short linear peptides which demonstrate good β-sheet folding and maintain bioactivity as in native B/PI. A library of 24 peptide 33mers (βpep-1 to βpep-24) were synthesized with various amino acid substitutions. CD and NMR data acquired in aqueous solution indicate that βpep peptides form β-sheet structure to varying degrees and self-associate as dimers and tetramers like the α-chemokines. Bactericidal activity toward Gram-negative Pseudomonas aeruginosa was tested, and βpep-19 was found to be only about 5-fold less potent (62% kill at 1.2×10?7 M) than native B/PI (80% kill at 2.9×10?8 M). At LPS neutralization, βpep-2 and -23 were found to be most active (66–78% effective at 1.2×10?6 M), being only about 50–100-fold less active than B/PI (50% at 1.5×10?8 M). In terms of structure–activity relations, β-sheet structural stability correlates with the capacity to neutralize LPS, but not with bactericidal activity. Although a net positive charge is necessary for activity, it is not sufficient for optimal activity. Hydrophobic residues tend to influence activities indirectly by affecting structural stability. Furthermore, results show that sequentially and spatially related residues from the β-sheet domain of native B/PI can be designed into short linear peptides which show good β-sheet folding and retain much of the native activity. This research contributes to the development of solutions to the problem of multiple drug-resistant, opportunistic microorganisms like P. aeruginosa and of agents effective at neutralizing bacterial endotoxin. 相似文献
912.
Athanassios Stavrakoudis Ioannis N. Demetropoulos Constantinos Sakarellos Maria Sakarellos-Daitsiotis Vassilios Tsikaris 《International journal of peptide research and therapeutics》1997,4(4-6):481-487
Summary The design, synthesis and catalytic properties of a cyclic branched peptide carrier that possesses the catalytic triad residues
of the serine proteases is reported. The synthesis of the peptide model was totally completed on solid support using three
different orthogonal amino protecting groups. Hydrolytic activity measurements against Suc-Ala-Ala-Ala-pNA substrate showed
that it is hydrolysed by the peptide model to a small extent. Despite this small hydrolytic activity, it is the first time,
to our knowledge, that hydrolysis of such a substrate is reported by an enzyme model compound. Contrary, this enzyme model
peptide showed considerable activity against the Boc-Ala-pNP substrate (k
cat
=0.414 min−1 andK
m
=0.228 mm). These results suggest that the designed carrier brings in appropriate contact the catalytic triad residues (Ser,
His, Asp) resulting in the obtained hydrolytic activity. 相似文献
913.
Formation of isoaspartate 99 in bovine and porcine somatotropins 总被引:4,自引:0,他引:4
Bernard N. Violand Michael R. Schlittler Paul C. Toren Ned R. Siegel 《Journal of Protein Chemistry》1990,9(1):109-117
Asparagine 99 in bovine (BST) and porcine somatotropins (PST) was converted to an isoaspartate residue during incubation at neutral or alkalinepH. Isoaspartate 99 BST or isoaspartate 99 PST was resolved from the normal somatotropin by reversed-phase high-performance liquid chromatography (HPLC). The altered peptide of residues 96–108 which contains isoaspartate 99 was detected by tryptic peptide mapping of the modified BST or PST. Amino acid sequencing, amino acid analysis, mass spectrometry, and co-elution with a chemically synthesized peptide containing isoaspartate 99 were used to demonstrate the existence of isoaspartate in the modified peptides. Peptide bond cleavage between Asn 99 and Ser 100 also occurred during incubation of BST and PST at neutral or alkalinepH. This chemically cleaved product was resolved on reversed-phase HPLC from both the isoaspartate 99 and normal somatotropin molecules. 相似文献
914.
TAR DNA结合蛋白43(transactive response DNA binding protein 43,TDP-43),一种可变剪切因子,可以特异性地结合富含TG序列的DNA,涉及多种神经退行性疾病. 分子动力学模拟方法虽然是研究分子间相互作用强有力的工具,但它非常耗时,且难以对有大的构象变化的体系进行充分采样来研究其变构行为. 本工作使用粗粒化的基于弹性势的高斯网络模型(Gaussian network model,GNM)研究人TDP-43与靶标DNA间相互作用的动力学. 进一步地,利用本课题组之前提出的基于GNM的热力学循环方法识别TDP-43与DNA相互作用的关键残基,其微扰引起了大的结合自由能的变化. DNA结合后,TDP-43上富含正电残基的loop1和loop3片段有较大的柔性损失,这反映了它们在识别和结合中的诱导契合作用. 另外发现,基于热力学循环的方法不仅识别到一些与DNA特异性相互作用有关的重要残基,而且识别到一些远离结合界面但在结合引起的分子构象变化中发挥重要作用的残基. 本研究有助于理解TDP-43与DNA的特异性相互作用,可为药物设计提供重要信息,另外该方法可以很方便地拓展到其他蛋白质-核酸相互作用动力学的研究. 相似文献