Synthesis of Hybrid Cyclopeptides through Enzymatic Macrocyclization.
Synthesis of Hybrid Cyclopeptides through Enzymatic Macrocyclization.
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DOI：
10.1002/open.201600134
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发表时间：
2017-02
期刊：
影响因子：
2.3
通讯作者：
Naismith JH
中科院分区：
文献类型：
--
作者：
Oueis E;Nardone B;Jaspars M;Westwood NJ;Naismith JH
天然产物包括各种各样的分子，其中许多具有生物活性。大多数天然产物来自聚酮化合物、肽、糖和脂肪酸结构单元的组合。肽大环化合物作为具有细胞渗透性、稳定性和易于控制的可变性的潜在治疗剂引起了人们的注意。在这里，我们表明，从patellamide生物合成途径的酶可以利用，使大环化合物的氨基酸和各种人造化学积木，包括芳环，聚醚和烷基链的杂交。我们已经制造了仅具有三个氨基酸的大环，其中一个可以转化为噻唑啉或噻唑环。我们报告了18个肽杂合大环化合物的合成，其中9个已被分离和充分表征。
Natural products comprise a diverse array of molecules, many of which are biologically active. Most natural products are derived from combinations of polyketides, peptides, sugars, and fatty‐acid building blocks. Peptidic macrocycles have attracted attention as potential therapeutics possessing cell permeability, stability, and easy‐to‐control variability. Here, we show that enzymes from the patellamide biosynthetic pathway can be harnessed to make macrocycles that are hybrids of amino acids and a variety of manmade chemical building blocks, including aryl rings, polyethers, and alkyl chains. We have made macrocycles with only three amino acids, one of which can be converted to a thiazoline or a thiazole ring. We report the synthesis of 18 peptide hybrid macrocycles, nine of which have been isolated and fully characterized.