Eric Koesema; Animesh Roy; Nicholas G. Paciaroni; Thomas Kodadek
Angew. Chem. Int. Ed. Engl., 2022, 61(18), e202116999
https://doi.org/10.1002/anie.202116999

Abstract

There is considerable interest in the development of libraries of non-peptidic macrocycles as a source of ligands for difficult targets. We report here the solid-phase synthesis of a DNA-encoded library of several hundred thousand thioether-linked macrocycles. The library was designed to be highly diverse with respect to backbone scaffold diversity and to minimize the number of amide N-H bonds, which compromise cell permeability. The utility of the library as a source of protein ligands is demonstrated through the isolation of compounds that bind streptavidin, a model target, with high affinity.