Yun Ding; Jing Chai; Paolo A. Centrella; Chenaimwoyo Gondo; Jennifer L. DeLorey; Matthew A. Clark
ACS Comb. Sci., 2018, 20, 5, 251-255
https://doi.org/10.1021/acscombsci.8b00009

Abstract

Encoded library technology (ELT) is an effective approach to the discovery of novel small-molecule ligands for biologi-cal targets. A key factor for the success of the technology is the chemical diversity of the libraries. Here we report the development of DNA-conjugated benzimidazoles. Using 4-fluoro-3-nitrobenzoic acid as a key synthon, we synthesized a 320 million-member DNA-encoded benzimidazole library using Fmoc-protected amino acids, amines and aldehydes as diversity elements. Affinity selection of the library led to the discovery of a novel, potent and specific antagonist of the NK3 receptor.