CEB-Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
LABBELS-Associate Laboratory, Braga/Guimarães, Portugal.
Biomolecules. 2023 Jun 12;13(6):981. doi: 10.3390/biom13060981.
This review provides a fresh overview of non-canonical amino acids and their applications in the design of peptidomimetics. Non-canonical amino acids appear widely distributed in nature and are known to enhance the stability of specific secondary structures and/or biological function. Contrary to the ubiquitous DNA-encoded amino acids, the structure and function of these residues are not fully understood. Here, results from experimental and molecular modelling approaches are gathered to classify several classes of non-canonical amino acids according to their ability to induce specific secondary structures yielding different biological functions and improved stability. Regarding side-chain modifications, symmetrical and asymmetrical α,α-dialkyl glycines, Cα to Cα cyclized amino acids, proline analogues, β-substituted amino acids, and α,β-dehydro amino acids are some of the non-canonical representatives addressed. Backbone modifications were also examined, especially those that result in retro-inverso peptidomimetics and depsipeptides. All this knowledge has an important application in the field of peptidomimetics, which is in continuous progress and promises to deliver new biologically active molecules and new materials in the near future.
这篇综述提供了对非天然氨基酸及其在肽模拟物设计中应用的最新概述。非天然氨基酸广泛存在于自然界中，已知可增强特定二级结构和/或生物功能的稳定性。与普遍存在的 DNA 编码氨基酸不同，这些残基的结构和功能尚未完全了解。在这里，根据它们诱导产生不同生物功能和提高稳定性的特定二级结构的能力，通过实验和分子建模方法的结果将几类非天然氨基酸进行分类。关于侧链修饰，对称和不对称的α,α-二烷基甘氨酸、Cα 到 Cα 环化氨基酸、脯氨酸类似物、β-取代氨基酸和α,β-脱氢氨基酸是一些被讨论的非天然氨基酸代表。还研究了骨架修饰，特别是导致反向肽模拟物和去肽的修饰。所有这些知识在肽模拟物领域都有重要的应用，该领域在不断发展，并有望在不久的将来提供新的具有生物活性的分子和新材料。
