Enzymatic Macrocyclization of 1,2,3-Triazole Peptide Mimetics.
Enzymatic Macrocyclization of 1,2,3-Triazole Peptide Mimetics.
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DOI：
10.1002/anie.201601564
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发表时间：
2016-05-04
期刊：
影响因子：
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通讯作者：
Naismith JH
中科院分区：
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作者：
Oueis E;Jaspars M;Westwood NJ;Naismith JH
线性肽的大环化通常伴随着其稳定性和生物活性的显著改善。许多策略可用于它们的化学大环化，然而，酶介导的方法在合成实用性方面仍然非常感兴趣。迄今为止，已知的大环化酶已被证明对肽和蛋白质底物都有活性。在这里，我们表明，大环化酶的cyanobactin家族，PatGmac，是能够大环化底物与一个，两个，或三个1，4-取代的1，2，3-三唑部分。在调节肽大环化合物的活性和物理性质时，将非肽支架引入大环化合物是非常理想的。我们已经分离并完全表征了9个非天然的含三唑环肽，还合成了另外10个分子。PatGmac现在已被证明是一种有效的和通用的工具，用于通过肽键形成闭环。
The macrocyclization of linear peptides is very often accompanied by significant improvements in their stability and biological activity. Many strategies are available for their chemical macrocyclization, however, enzyme‐mediated methods remain of great interest in terms of synthetic utility. To date, known macrocyclization enzymes have been shown to be active on both peptide and protein substrates. Here we show that the macrocyclization enzyme of the cyanobactin family, PatGmac, is capable of macrocyclizing substrates with one, two, or three 1,4‐substituted 1,2,3‐triazole moieties. The introduction of non‐peptidic scaffolds into macrocycles is highly desirable in tuning the activity and physical properties of peptidic macrocycles. We have isolated and fully characterized nine non‐natural triazole‐containing cyclic peptides, a further ten molecules are also synthesized. PatGmac has now been shown to be an effective and versatile tool for the ring closure by peptide bond formation.