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Synthesis and Screening of a DNA-Encoded Library of Non-Peptidic Macrocycles.

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.

SUBMITTER: Koesema E

PROVIDER: S-EPMC9285660 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Synthesis and Screening of a DNA-Encoded Library of Non-Peptidic Macrocycles.

Koesema Eric E Roy Animesh A Paciaroni Nicholas G NG Coito Carlos C Tokmina-Roszyk Michal M Kodadek Thomas T

Angewandte Chemie (International ed. in English) 20220302 18

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 demon ...[more]

PMID: 35192245

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