Choi Soo Hyuk, Guzei Ilia A, Spencer Lara C, Gellman Samuel H
Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
J Am Chem Soc. 2008 May 21;130(20):6544-50. doi: 10.1021/ja800355p. Epub 2008 Apr 26.
Oligomers that contain both alpha- and beta-amino acid residues in a 1:1 alternating pattern have recently been shown by several groups to adopt helical secondary structures in solution. The beta-residue substitution pattern has a profound effect on the type of helix formed and the stability of the helical conformation. On the basis of two-dimensional NMR data, we have previously proposed that beta-residues with a five-membered ring constraint promote two different types of alpha/beta-peptide helix. The "11-helix" contains i, i+3 CO...H-N hydrogen bonds between backbone amide groups; these hydrogen bonds occur in 11-atom rings. The alpha/beta-peptide "14/15-helix" contains i, i+4 CO...H-N hydrogen bonds, which occur in alternating 14- and 15-atom rings. Here we provide crystallographic data for 14 alpha/beta-peptides that form the 11-helix and/or the 14/15-helix. These results were obtained for a series of oligomers containing beta-residues derived from ( S,S)- trans-2-aminocyclopentanecarboxylic acid (ACPC) and alpha-residues derived from alpha-aminoisobutyric acid (Aib) or l-alanine (Ala). The crystallized alpha/beta-peptides range in length from 4 to 10 residues. Nine of the alpha/beta-peptides display the 11-helix in the solid state, three display the 14/15-helix, and two display conformations that contain both i, i+3 and i, i+4 CO...H-N hydrogen bonds, but not bifurcated hydrogen bonds. Only 3 of the 14 crystal structures presented here have been previously described. These results suggest that longer alpha/beta-peptides prefer the 14/15-helix over the 11-helix, a conclusion that is consistent with previously reported NMR data obtained in solution.
最近有几个研究小组表明，以1:1交替模式同时包含α-和β-氨基酸残基的寡聚体在溶液中会形成螺旋二级结构。β-残基的取代模式对所形成螺旋的类型和螺旋构象的稳定性有深远影响。基于二维核磁共振数据，我们之前曾提出，具有五元环限制的β-残基会促进两种不同类型的α/β-肽螺旋的形成。“11-螺旋”在主链酰胺基团之间包含i、i + 3 CO…H-N氢键；这些氢键出现在11原子环中。α/β-肽“14/15-螺旋”包含i、i + 4 CO…H-N氢键，它们出现在交替的14和15原子环中。在此，我们提供了14种形成11-螺旋和/或14/15-螺旋的α/β-肽的晶体学数据。这些结果是针对一系列寡聚体获得的，这些寡聚体包含源自（S,S）-反式-2-氨基环戊烷羧酸（ACPC）的β-残基和源自α-氨基异丁酸（Aib）或L-丙氨酸（Ala）的α-残基。结晶的α/β-肽长度范围为4至10个残基。其中9种α/β-肽在固态下呈现11-螺旋，3种呈现14/15-螺旋，2种呈现同时包含i、i + 3和i、i + 4 CO…H-N氢键但没有分叉氢键的构象。此处展示的14个晶体结构中只有3个先前已有描述。这些结果表明，较长的α/β-肽比较短的α/β-肽更倾向于形成14/15-螺旋而非11-螺旋，这一结论与先前在溶液中获得的核磁共振数据一致。
