Control of hairpin formation via proline configuration in parallel β-sheet model systems
Control of hairpin formation via proline configuration in parallel β-sheet model systems
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DOI：
10.1021/ja9929483
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发表时间：
2000-06-14
影响因子：
15
通讯作者：
Gellman, SH
中科院分区：
文献类型：
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作者：
Fisk, JD;Powell, DR;Gellman, SH
创建平行 β-折叠模型系统的最简单策略是通过 N 末端或 C 末端连接相邻的肽链。这种连接需要不自然的连接段。我们描述了可以作为 N-N 或 C-to-C 连接体的二肽模拟物，并通过氯仿中四肽类似物的构象分析证明了它们的功效。四肽类似物可采用链-环-链(“发夹”)构象，其中每个末端的残基L-缬氨酸和L-亮氨酸参与平行片氢键相互作用。我们的接头含有脯氨酸残基，以赋予优选的局部扭曲。我们表明，含有 D-脯氨酸的接头促进链 L-残基之间的平行片相互作用，而含有 L-脯氨酸的接头不促进平行片相互作用。对一种接头扭曲的偏好可能与蛋白质β-折叠中的链显示的右手扭曲有关（平行和反平行）；在反平行β-折叠模型系统中观察到了类似的接头扭曲偏好。
The simplest strategy for creation of parallel beta-sheet model systems is to link adjacent peptide strands via their N-termini or via their C-termini. This connectivity requires unnatural linking segments. We describe dipeptide mimics that can serve as N-to-N or C-to-C: linkers, and we demonstrate their efficacy by conformational analysis of tetrapeptide analogues in chloroform. The tetrapeptide analogues can adopt strand-loop-strand ("hairpin") conformations in which the residues at each end, L-valine and L-leucine, engage in parallel sheet hydrogen bonding interactions. Our linkers contain proline residues, to impart a preferred local twist. We show that linkers containing D-proline promote parallel sheet interactions between the strand L-residues, while linkers containing L-proline do not promote parallel sheet interactions. The preference for one linker twist is presumably related to the right-handed twist displayed by strands in protein beta-sheets (parallel and antiparallel); analogous linker twist preferences have been observed in antiparallel beta-sheet model systems.