Kawakami Takashi, Ohta Atsushi, Ohuchi Masaki, Ashigai Hiroshi, Murakami Hiroshi, Suga Hiroaki
Department of Chemistry and Biotechnology, The University of Tokyo, Japan.
Nat Chem Biol. 2009 Dec;5(12):888-90. doi: 10.1038/nchembio.259. Epub 2009 Oct 25.
We report a methodology for the ribosomal synthesis of backbone-cyclized peptides involving genetic code reprogramming to introduce one or more nonproteinogenic amino acids. Expression of linear peptides bearing a cysteine-proline dipeptide sequence followed by glycolic acid results in self-rearrangement to a C-terminal diketopiperadine-thioester, which non-enzymatically generates a cyclized peptide. We demonstrate the ribosomal synthesis of several naturally occurring backbone-cyclized peptides and a library based on a bicyclic scaffold, and we identify bioactive sequences by screening and deconvolution.
我们报告了一种用于核糖体合成主链环化肽的方法，该方法涉及遗传密码重编程以引入一种或多种非蛋白质ogenic氨基酸。带有半胱氨酸-脯氨酸二肽序列并随后连接乙醇酸的线性肽的表达导致自重排为C端二酮哌嗪硫酯，其非酶促生成环化肽。我们展示了几种天然存在的主链环化肽和基于双环支架的文库的核糖体合成，并通过筛选和解卷积鉴定了生物活性序列。
