Oueis Emilia, Jaspars Marcel, Westwood Nicholas J, Naismith James H
Biomedical Science Research Complex University of St Andrews, BSRC North Haugh St Andrews KY16 9ST UK.
Marine Biodiscovery Centre, Department of Chemistry University of Aberdeen Old Aberdeen AB24 3UE UK.
Angew Chem Weinheim Bergstr Ger. 2016 May 4;128(19):5936-5939. doi: 10.1002/ange.201601564. Epub 2016 Apr 5.
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.
线性肽的大环化常常伴随着其稳定性和生物活性的显著提高。有许多策略可用于其化学大环化，然而，就合成实用性而言，酶介导的方法仍然备受关注。迄今为止，已知的大环化酶已被证明对肽和蛋白质底物均具有活性。在此我们表明，蓝细菌素家族的大环化酶PatGmac能够使带有一个、两个或三个1,4-取代的1,2,3-三唑部分的底物发生大环化。将非肽类支架引入大环对于调节肽类大环的活性和物理性质非常有必要。我们已经分离并全面表征了九个含非天然三唑的环肽，还合成了另外十个分子。现已证明，PatGmac是通过肽键形成实现闭环的一种有效且通用的工具。
