Stereochemical control of hairpin formation in β-peptides containing dinipecotic acid reverse turn segments
Stereochemical control of hairpin formation in β-peptides containing dinipecotic acid reverse turn segments
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DOI：
10.1021/ja993416p
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发表时间：
2000-05-03
影响因子：
15
通讯作者：
Gellman, SH
中科院分区：
文献类型：
--
作者：
Chung, YJ;Huck, BR;Gellman, SH
我们研究了一系列β-氨基酸四聚体的共价结构和构象倾向之间的关系。这些实验的重点是发夹折叠主题。在传统的多肽中，β-折叠二级结构的最小增量是“β-发夹”，即两条链通过一个短环连接。本研究旨在优化β-多肽的发夹稳定性。我们实验室以前的工作已经确定了在反平行的β-肽片中形成链的残基的最佳替代模式(Krauthauser等人)。J.Am化学。秒。1997年、119、11719)，我们已经证明二尼克酸片段可以促进连接的链残基之间的片状相互作用(Chung等人。J.Ant.化学。秒。1998年、120、10555)。在这里，我们比较了二异丙酸片段的所有四种可能的构型，(R，S)，(S，R)，(R，R)和(S，S)，以诱导具有恒定的一组对映体纯链残基的片层形成的能力。我们表明，两个异手性二异丙酸片段都促进发夹的形成，尽管其中一个明显优越。这两种同型手性二磷酸都不支持发夹折叠。当链残基为β-丙氨酸(非手性)时，异手性二异丙酸片段再次优于同手性片段，但我们发现发夹构象在溶液中和固体中不同。
We examine the relationship between covalent structure and conformational propensity among a series of beta-amino acid tetramers. These experiments focus on the hairpin folding motif. Among conventional peptides, the minimum increment of beta-sheet secondary structure is a "beta-hairpin," in which two strands are connected via a short loop. The present studies are aimed at optimizing hairpin stability among beta-peptides. Previous work from our laboratory has identified optimal substitution patterns for residues that form strands in an antiparallel beta-peptide sheet (Krauthauser et al. J. Am. Chem. Sec. 1997, 119, 11719), and we have shown that a dinipecotic acid segment can promote sheet-type interactions between attached strand residues (Chung et al. J. Ant. Chem. Sec. 1998, 120, 10555). Here we compare all four possible configurations of the dinipecotic acid segment, (R,S), (S,R), (R,R) and (S,S), for the ability to induce sheet formation with a constant set of enantiomerically pure strand residues. We show that both heterochiral dinipecotic acid segments promote hairpin formation, although one is distinctly superior. Neither of the homochiral dinipecotic acid supports hairpin folding. When the strand residues are beta-alanine (achiral), the heterochiral dinipecotic acid segment is again superior to the homochiral segment, but we find a difference between hairpin conformations in solution and in the solid state.