Cylindrical β-sheet peptide assemblies

被引:179
作者
Clark, TD
Buriak, JM
Kobayashi, K
Isler, MP
McRee, DE
Ghadiri, MR
机构
[1] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA
[2] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA
[3] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA
关键词
D O I
10.1021/ja981485i
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
引用
收藏
页码:8949 / 8962
页数:14
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