Tolerance of acyclic residues in the beta-peptide 12-helix: access to diverse side-chain arrays for biological applications.
Tolerance of acyclic residues in the beta-peptide 12-helix: access to diverse side-chain arrays for biological applications.
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β 肽 12 螺旋中无环残基的耐受性：获得用于生物应用的不同侧链阵列。
DOI：
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发表时间：
2002
影响因子：
15
通讯作者：
S. Gellman
中科院分区：
文献类型：
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作者：
P. LePlae;J. D. Fisk;E. A. Porter;B. Weisblum;S. Gellman
具有明确构象倾向的寡聚主链可以作为支架，以特定的三维排列展示官能团组。 β 肽在这方面特别令人感兴趣，因为通过适当选择 β 氨基酸取代模式可以诱导几种不同的二级结构。3 β 肽 12 螺旋（由 12 元环 C=O(i)- -H-N(i + 3) 氢键定义）特别令人感兴趣，因为该螺旋类似于 α 螺旋。迄今为止，已在仅由含有五元环约束的残基组成的 β 肽中观察到 12 螺旋。在这里，我们表明，当一些环状 β-氨基酸残基被更灵活的无环残基取代时，12 螺旋倾向得以保持。这个结果很重要，因为无环残基的使用极大地促进了沿着 12 螺旋的特定位点引入不同侧链。我们展示了这一进步在抗生素设计中的实用性。
Oligomeric backbones with well-defined conformational propensities can serve as scaffolds for displaying sets of functional groups in specific three-dimensional arrangements. beta-Peptides are particularly interesting in this regard because several distinct secondary structures can be induced by appropriate choice of beta-amino acid substitution pattern.3 The beta-peptide 12-helix (defined by 12-membered ring C=O(i)- -H-N(i + 3) hydrogen bonds) is of particular interest because this helix resembles the alpha-helix. To date 12-helices have been observed in beta-peptides comprised exclusively of residues containing a five-membered ring constraint. Here we show that 12-helical propensity is maintained when some cyclic beta-amino acid residues are replaced with more flexible acyclic residues. This result is important because use of acyclic residues greatly facilitates introduction of diverse side chains at specific sites along the 12-helix. We demonstrate the utility of this advance in the context of antibiotic design.