Ribosome-mediated synthesis of natural product-like peptides via cell-free translation.

Rumit Maini, Shiori Umemoto, Hiroaki Suga

Journal: Current opinion in chemical biology 2017;34():44-52

PMID: 27344230

Full Text on Elsevier Science View on PubMed

Abstract

Peptide natural products (PNPs) represent a unique class of compounds known for their fascinating structural motifs with important biological activities. Lately, PNPs have garnered a lot of interest for their application in drug discovery. Nevertheless, lack of diversity oriented synthetic/biosynthetic platforms to generate large natural product-like libraries has limited their development as peptide therapeutics. The promiscuity of cell-free translation has allowed for the synthesis of artificial PNPs having complex structural features. Modified cell-free translation systems coupled with the display technologies have generated diverse natural product-like peptide libraries and led to the discovery of several biologically active molecules. Such technologies have drastically decreased the time to obtain peptide drug leads and therefore, revolutionized the field of peptide drug discovery. In this account, we review recent developments in the synthesis of natural product-like peptides via cell-free translation.

Address: Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.; Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; JST, CREST, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Electronic address: [email protected].

DOI: 10.1016/j.cbpa.2016.06.006

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MeSH Terms: Amino Acids, Biological Products, Cell-Free System, Cyclization, Peptides, Protein Biosynthesis, Ribosomes