Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
Curr Opin Chem Biol. 2011 Jun;15(3):355-61. doi: 10.1016/j.cbpa.2011.03.009. Epub 2011 Apr 12.
The genetic encoding of polypeptides with biological display systems enables the facile generation and screening of very large combinatorial libraries of molecules. By post-translationally modifying the encoded polypeptides, chemically and structurally more diverse molecules beyond linear amino acid polymers can be generated. The first post-translational modification applied to encoded polypeptides, the oxidation of cysteine residues to form disulfide bridges, is a natural one and was used to cyclise short peptides soon after the invention of phage display. Recently a range of non-natural chemical strategies for the post-translational modification of encoded polypeptide repertoires were applied to generate optical biosensors, semisynthetic polypeptides, peptide-drug conjugates, redox-insensitive monocyclic peptides or multicyclic peptides, and these strategies are reviewed in this article.
生物展示系统对多肽的遗传编码使非常大的分子组合文库的生成和筛选变得非常容易。通过对编码多肽进行翻译后修饰，可以生成比线性氨基酸聚合物更具化学和结构多样性的分子。第一个应用于编码多肽的翻译后修饰是半胱氨酸残基的氧化形成二硫键，这是一种天然的修饰，并且在噬菌体展示发明后不久就被用于环化短肽。最近，一系列非天然的化学策略被应用于翻译后修饰编码多肽库，以生成光学生物传感器、半合成多肽、肽药物偶联物、氧化还原不敏感的单环肽或多环肽，本文对这些策略进行了综述。
