Second-generation DNA-templated macrocycle libraries for the discovery of bioactive small molecules.

ABSTRACT: DNA-encoded libraries have emerged as a widely used resource for the discovery of bioactive small molecules, and offer substantial advantages compared with conventional small-molecule libraries. Here, we have developed and streamlined multiple fundamental aspects of DNA-encoded and DNA-templated library synthesis methodology, including computational identification and experimental validation of a 20 × 20 × 20 × 80 set of orthogonal codons, chemical and computational tools for enhancing the structural diversity and drug-likeness of library members, a highly efficient polymerase-mediated template library assembly strategy, and library isolation and purification methods. We have integrated these improved methods to produce a second-generation DNA-templated library of 256,000 small-molecule ma

SUBMITTER: Usanov DL 

PROVIDER: S-EPMC6014893 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature