Ribosomal synthesis of polypeptoids and peptoid-peptide hybrids.
Here we report a new methodology for mRNA-programmed synthesis of peptoids and peptoid-peptide hybrids by means of translation machinery under the reprogrammed genetic code. We initially screened N-substituted glycines (rGly) for their single incorporation into a nascent peptide chain and found translation machinery accepts a variety of rGly for elongation. Moreover, we have shown consecutive elongations of rGly and mRNA-directed synthesis of cyclic peptoid-peptide hybrids. This methodology offers a powerful tool for mRNA-programmed library synthesis of peptoids and peptoid-peptide hybrids with linear and cyclic scaffolds, potentially leading to the discovery of drug candidates with proteolytic stability and membrane permeability.
Kawakami
Takashi
T
Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.
Murakami
Hiroshi
H
Suga
Hiroaki
H
D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D012270:Ribosomes / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D010455:Peptides; D012333:RNA, Messenger