Cylindrical β-sheet peptide assemblies
Cylindrical β-sheet peptide assemblies
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DOI：
10.1021/ja981485i
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发表时间：
1998-09-09
影响因子：
15
通讯作者：
Ghadiri, MR
中科院分区：
文献类型：
--
作者：
Clark, TD;Buriak, JM;Ghadiri, MR
最近的研究表明，由偶数个交替的D-和l -氨基酸组成的环肽可以采用扁平的圆盘状构象，并通过骨干-骨干氢键堆叠形成延伸的纳米管结构。目前的工作详细介绍了通过主链烷基化限制这种自组装过程的一般策略，从而产生圆柱形β -片肽二聚体。通过核磁共振、红外光谱、质谱和x射线晶体学研究，研究了20个环肽在环大小、主链烷基取代基的位置和身份以及氨基酸组成方面的变化，研究了二聚化的范围和局限性。环状肽在溶液和固体状态下都可以通过预期的反平行β -片氢键网络自组装。虽然环八肽的溶液二聚化现象普遍存在，但具有较小或较大环尺寸的肽不能自结合。发现圆柱形β -片群的形成可以容忍许多主干n-烷基取代基，包括甲基、烯丙基、正丙基和戊-4-烯-1-基，以及一系列氨基酸侧链。在半n -甲基化八肽框架内，残基表现出二聚体稳定的不同倾向，类似于自然系统中的氨基酸β -片倾向。因此，二聚体形成的环D， l肽是结构上表征最充分、最容易合成的β -片肽模型体系之一。
Recent reports have shown that cyclic peptides composed of an even number of alternating D- and L-amino acids can adopt flat, disklike conformations and stack through backbone-backbone hydrogen-bonding to form extended nanotubular structures. The present work details a general strategy for limiting this self-assembly process through backbone alkylation, giving rise to cylindrical beta-sheet peptide dimers. Scope and limitations of dimerization are examined through NMR, FT-IR, mass spectral, and X-ray crystallographic studies of 20 cyclic peptides varying in ring size, location and identity of backbone alkyl substituents, and amino acid composition. The cyclic peptides are shown to self-assemble both in solution and in the solid state through the expected antiparallel beta-sheet hydrogen-bonding network. While solution dimerization by cyclic octapeptides appears general, peptides with alternative smaller or larger ring sizes fail to self-associate. Formation of cylindrical beta-sheet ensembles is found to tolerate a number of backbone N-alkyl substituents, including methyl, allyl, n-propyl, and pent-4-en-1-yl groups, as well as a range of amino acid side chains. Within the hemi-N-methylated octapeptide framework, residues exhibit differential propensities for dimer stabilization, analogous to amino acid beta-sheet propensities in natural systems. Dimer-forming cyclic D,L-peptides are thus among the most structurally well characterized and synthetically accessible beta-sheet peptide model systems.