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Display Selection of Exotic Macrocyclic Peptides Expressed under a Radically Reprogrammed 23 Amino Acid Genetic Code.

Display Selection of Exotic Macrocyclic Peptides Expressed under a Radically Reprogrammed 23 Amino Acid Genetic Code.

Authors :
Passioura T
Liu W
Dunkelmann D
Higuchi T
Suga H
Source :
Journal of the American Chemical Society [J Am Chem Soc] 2018 Sep 19; Vol. 140 (37), pp. 11551-11555. Date of Electronic Publication: 2018 Sep 04.
Publication Year :
2018

Abstract

Bioactive naturally occurring macrocyclic peptides often exhibit a strong bias for hydrophobic residues. Recent advances in in vitro display technologies have made possible the identification of potent macrocyclic peptide ligands to protein targets of interest. However, such approaches have so far been restricted to using libraries composed of peptides containing mixtures of hydrophobic and hydrophilic/charged amino acids encoded by the standard genetic code. In the present study, we have demonstrated ribosomal expression of exotic macrocyclic peptides under a radically reprogrammed, relatively hydrophobic, genetic code, comprising 12 proteinogenic and 11 nonproteinogenic amino acids. Screening of this library for affinity to the interleukin-6 receptor (IL6R) as a case study successfully identified exotic macrocyclic peptide ligands with high affinity, validating the feasibility of this approach for the discovery of relatively hydrophobic exotic macrocyclic peptide ligands.

Details

Language :
English
ISSN :
1520-5126
Volume :
140
Issue :
37
Database :
MEDLINE
Journal :
Journal of the American Chemical Society
Publication Type :
Academic Journal
Accession number :
30157372
Full Text :
https://doi.org/10.1021/jacs.8b03367