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Ribosomal Natural Products, Tailored To Fit
Accounts of Chemical Research ( IF 16.4 ) Pub Date : 2017-07-06 00:00:00 , DOI: 10.1021/acs.accounts.7b00175 Michael A. Funk 1 , Wilfred A. van der Donk 1
Accounts of Chemical Research ( IF 16.4 ) Pub Date : 2017-07-06 00:00:00 , DOI: 10.1021/acs.accounts.7b00175 Michael A. Funk 1 , Wilfred A. van der Donk 1
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Ribosomally synthesized and Post-translationally modified Peptides (RiPPs) take advantage of the ribosomal translation machinery to generate linear peptides that are subsequently modified with heterocycles and/or macrocycles to impose three-dimensional structure and thwart degradation by proteases. Although RiPP precursors are limited to proteinogenic amino acids, post-translational modifications (PTMs) can alter the structure of individual amino acids and thereby improve the stability and biological activity of the molecule. These “tailoring modifications” often occur on amino acid side chains—for example, hydroxylation, methylation, halogenation, prenylation, and acylation—but can also take place within the backbone, as in epimerization, or can result in capping of the N- or C-terminus. At one extreme, these modifications can be essential to the activity of the RiPP, either as a compulsory step in reaching the final molecule or by imparting chemical functionality required for biological activity. At the other extreme, tailoring PTMs may have little effect on the activity in an in vitro setting—possibly because of test conditions that do not match the biological context in which the PTMs evolved.
中文翻译：
核糖体天然产品，量身定制
里bosomally合成和P OST-翻译后修饰P肽（RiPP）利用核糖体翻译机制来生成线性肽，随后用杂环和/或大环修饰这些线性肽，从而施加三维结构并阻止蛋白酶降解。尽管RiPP前体仅限于蛋白原氨基酸，但翻译后修饰（PTM）可以改变单个氨基酸的结构，从而提高分子的稳定性和生物活性。这些“定制修饰”通常发生在氨基酸侧链上，例如羟基化，甲基化，卤化，异戊烯化和酰化，但也可能发生在主链内，如差向异构化，或导致N-或N-或N-或N-或N-或N-或N-或N-或N-或N-或N-或N-的封端。 C末端。在一个极端情况下，这些修改对于RiPP的活动可能是必不可少的，作为到达最终分子的强制性步骤，或者通过赋予生物活性所需的化学功能性进行。在另一个极端，量身定制的PTM在体外环境中对活性的影响可能很小-可能是因为测试条件与PTM进化的生物学环境不匹配。
更新日期：2017-07-06
中文翻译：
核糖体天然产品，量身定制
里bosomally合成和P OST-翻译后修饰P肽（RiPP）利用核糖体翻译机制来生成线性肽，随后用杂环和/或大环修饰这些线性肽，从而施加三维结构并阻止蛋白酶降解。尽管RiPP前体仅限于蛋白原氨基酸，但翻译后修饰（PTM）可以改变单个氨基酸的结构，从而提高分子的稳定性和生物活性。这些“定制修饰”通常发生在氨基酸侧链上，例如羟基化，甲基化，卤化，异戊烯化和酰化，但也可能发生在主链内，如差向异构化，或导致N-或N-或N-或N-或N-或N-或N-或N-或N-或N-或N-或N-的封端。 C末端。在一个极端情况下，这些修改对于RiPP的活动可能是必不可少的，作为到达最终分子的强制性步骤，或者通过赋予生物活性所需的化学功能性进行。在另一个极端，量身定制的PTM在体外环境中对活性的影响可能很小-可能是因为测试条件与PTM进化的生物学环境不匹配。
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