Affinity selection of double-click triazole libraries for rapid discovery of allosteric modulators for GLP-1 receptor.

ABSTRACT: The recently developed double-click reaction sequence [G. Meng et al., Nature 574, 86-89 (2019)] is expected to vastly expand the number and diversity of synthetically accessible 1,2,3-triazole derivatives. However, it remains elusive how to rapidly navigate the extensive chemical space created by double-click chemistry for bioactive compound discovery. In this study, we selected a particularly challenging drug target, the glucagon-like-peptide-1 receptor (GLP-1R), to benchmark our new platform for the design, synthesis, and screening of double-click triazole libraries. First, we achieved a streamlined synthesis of customized triazole libraries on an unprecedented scale (composed of 38,400 new compounds). By interfacing affinity-selection mass spectrometry and function

SUBMITTER: Xin Y 

PROVIDER: S-EPMC10243133 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature