Nonproteinogenic amino acid building blocks for nonribosomal peptide and hybrid polyketide scaffolds.
Nonproteinogenic amino acid building blocks for nonribosomal peptide and hybrid polyketide scaffolds.
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DOI：
10.1002/anie.201208344
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发表时间：
2013-07-08
期刊：
影响因子：
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通讯作者：
Khosla C
中科院分区：
文献类型：
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作者：
Walsh CT;O'Brien RV;Khosla C
长期以来，人们一直认为独立的非蛋白生成氨基酸具有抗代谢的特性，而且容易被靶标酶的催化作用所揭示的反应功能所取代。通过将它们特异性地安装到生物源多肽和蛋白质中，可能会在小分子和大分子药物化学的界面上开创一个新纪元。位点选择性蛋白质功能化为蛋白质的翻译后修饰提供了独特的有吸引力的策略。最后但并非最不重要的一点是，在核糖体衍生多肽的背景下，许多不是自然界中选择用于蛋白质掺入的氨基酸提供了丰富的结构可能性。本文综述了在非核糖体肽骨架和杂化非核糖体肽-聚酮支架中形成的主要非正则氨基酸构建块的生物合成途径和代谢逻辑。
Freestanding nonproteinogenic amino acids have long been recognized for their antimetabolite properties and tendency to be uncovered to reactive functionalities by the catalytic action of target enzymes. By installing them regiospecifically into biogenic peptides and proteins, it may be possible to usher a new era at the interface between small molecule and large molecule medicinal chemistry. Site‐selective protein functionalization offers uniquely attractive strategies for posttranslational modification of proteins. Last, but not least, many of the amino acids not selected by nature for protein incorporation offer rich architectural possibilities in the context of ribosomally derived polypeptides. This Review summarizes the biosynthetic routes to and metabolic logic for the major classes of the noncanonical amino acid building blocks that end up in both nonribosomal peptide frameworks and in hybrid nonribosomal peptide‐polyketide scaffolds.