Screening of protein-protein interaction modulators via sulfo-click kinetic target-guided synthesis.

ABSTRACT: Kinetic target-guided synthesis (TGS) and in situ click chemistry are among unconventional discovery strategies having the potential to streamline the development of protein-protein interaction modulators (PPIMs). In kinetic TGS and in situ click chemistry, the target is directly involved in the assembly of its own potent, bidentate ligand from a pool of reactive fragments. Herein, we report the use and validation of kinetic TGS based on the sulfo-click reaction between thio acids and sulfonyl azides as a screening and synthesis platform for the identification of high-quality PPIMs. Starting from a randomly designed library consisting of 9 thio acids and 9 sulfonyl azides leading to 81 potential acylsulfonamides, the target protein, Bcl-X(L), selectively assembled four PPIMs, acylsulfonami

SUBMITTER: Kulkarni SS 

PROVIDER: S-EPMC3151735 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature