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

Journal of the American Chemical Society
Toby PassiouraHiroaki Suga

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.

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Citations

Nov 27, 2018·Natural Product Reports·Robert A Hill, Andrew Sutherland
Aug 15, 2020·Chembiochem : a European Journal of Chemical Biology·Donghyeok Gang, Hee-Sung Park
Oct 30, 2020·Frontiers in Bioengineering and Biotechnology·Zhenling CuiKirill Alexandrov
Feb 4, 2021·ACS Chemical Biology·Grégoire J-B PhilippeSónia T Henriques
Jan 23, 2021·ACS Chemical Biology·Mariha IslamJames A Van Deventer
Apr 12, 2019·Current Opinion in Biotechnology·Arlinda RezhdoJames A Van Deventer
Mar 19, 2021·Journal of the American Chemical Society·Masanobu NaganoHiroaki Suga
Feb 1, 2020·Molecular Systems Design & Engineering·K A PottsJ A Van Deventer
Jun 29, 2021·RSC Chemical Biology·Joseph M RogersAshraf Brik
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Wei WangDian Su
Feb 16, 2019·Journal of the American Chemical Society·Alexander A VinogradovHiroaki Suga
Nov 11, 2020·ACS Combinatorial Science·Sabrina E IskandarAlbert A Bowers
Aug 7, 2019·The Journal of Organic Chemistry·Diego Alemán-Ponce de LeónLuis A Polindara-García
Nov 6, 2018·Chemical Reviews·Yichao HuangHiroaki Suga

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