Diverse Backbone-cyclized Peptides Via Codon Reprogramming

Overview

Journal Nat Chem Biol

Specialties Biochemistry
Biology
Chemistry

Date 2009 Nov 17

PMID 19915537

Citations 49

Authors

Takashi Kawakami

Atsushi Ohta

Masaki Ohuchi

Hiroshi Ashigai

Hiroshi Murakami

Hiroaki Suga

Affiliations

Soon will be listed here.

Abstract

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.

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