An efficient method for the in vitro production of azol(in)e-based cyclic peptides.
An efficient method for the in vitro production of azol(in)e-based cyclic peptides.
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DOI：
10.1002/anie.201408082
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发表时间：
2014-12-15
影响因子：
16.6
通讯作者：
Jaspars, Marcel
中科院分区：
文献类型：
--
作者：
Houssen, Wael E.;Bent, Andrew F.;McEwan, Andrew R.;Pieiller, Nathalie;Tabudravu, Jioji;Koehnke, Jesko;Mann, Greg;Adaba, Rosemary I.;Thomas, Louise;Hawas, Usama W.;Liu, Huanting;Schwarz-Linek, Ulrich;Smith, Margaret C. M.;Naismith, James H.;Jaspars, Marcel
含杂环的环肽是一种很有前途的药物支架材料，但其化学合成却极具挑战性。已经设计了一种新的通用方法来制备这些化合物，通过使用一组工程化的海洋衍生的酶和底物，这些酶和底物从被称为蓝藻菌素的核糖体产生和后修饰的肽家族获得。底物前体肽被工程化以具有可被快速切割的非天然蛋白酶切割位点。使用的其他酶是将Cys或Cys/Ser/Thr转化成其相应的唑啉的杂环酶。使用大环化酶形成大环，然后用特异性氧化酶将唑啉氧化成唑。该工作的例子是生产17个大环，含有6-9个残基，代表20个典型氨基酸中的11个。
Heterocycle-containing cyclic peptides are promising scaffolds for the pharmaceutical industry but their chemical synthesis is very challenging. A new universal method has been devised to prepare these compounds by using a set of engineered marine-derived enzymes and substrates obtained from a family of ribosomally produced and post-translationally modified peptides called the cyanobactins. The substrate precursor peptide is engineered to have a non-native protease cleavage site that can be rapidly cleaved. The other enzymes used are heterocyclases that convert Cys or Cys/Ser/Thr into their corresponding azolines. A macrocycle is formed using a macrocyclase enzyme, followed by oxidation of the azolines to azoles with a specific oxidase. The work is exemplified by the production of 17 macrocycles containing 6–9 residues representing 11 out of the 20 canonical amino acids.
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影响因子：
4.4
作者：
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通讯作者：
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影响因子：
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作者：
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核糖体途径到小分子多样性。
影响因子：
15
作者：
Tianero, Ma Diarey B.;Donia, Mohamed S.;Young, Travis S.;Schultz, Peter G.;Schmidt, Eric W.
通讯作者：
Schmidt, Eric W.
影响因子：
14.8
作者：
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通讯作者：
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