Higgins K A, Thompson P E, Hearn M T
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
Int J Pept Protein Res. 1996 Jul;48(1):1-11. doi: 10.1111/j.1399-3011.1996.tb01101.x.
The conformational analysis of a series of ten hGH[6-13] peptide analogues is reported. As part of our earlier studies, the alpha-aminosuccinimide modified fragment Asu11-hGH[6-13] has previously been identified as a potentiator of insulin activity in intravenous insulin tolerance tests, and various analogues have been subsequently designed, synthesised and employed to acquire structure-activity data. These studies have lead to the conclusion that the conformational characteristics at the C-terminus of each of the active peptide analogues is important to the biological activity. In the present investigation, molecular dynamics and simulated annealing techniques have been used to examine the accessible conformational states of the C-terminal region of ten different hGH[6-13] peptide analogues. Of these six are active peptide analogues while the other four show no biological activity. Examination of the conformer groups identified using this molecular dynamics approach showed a common conformational motif for each of the active peptides.
报道了一系列十种hGH[6-13]肽类似物的构象分析。作为我们早期研究的一部分，α-氨基琥珀酰亚胺修饰的片段Asu11-hGH[6-13]先前已被确定为静脉胰岛素耐量试验中胰岛素活性的增强剂，随后设计、合成并使用了各种类似物来获取构效关系数据。这些研究得出的结论是，每种活性肽类似物C末端的构象特征对生物活性很重要。在本研究中，分子动力学和模拟退火技术已被用于研究十种不同hGH[6-13]肽类似物C末端区域的可及构象状态。其中六种是活性肽类似物，而其他四种没有生物活性。使用这种分子动力学方法鉴定的构象组检查显示，每种活性肽都有一个共同的构象基序。
