Small Molecule Probes That Perturb A Protein-protein Interface In Antithrombin.

ABSTRACT: Small molecule probes for perturbing protein-protein interactions (PPIs) in vitro can be useful if they cause the target proteins to undergo biomedically relevant changes to their tertiary and quaternary structures. Application of the Exploring Key Orientations (EKO) strategy (J. Am. Chem. Soc., 2013, 135, 167 - 173) to a piperidinone-piperidine chemotype 1 indicated specific derivatives were candidates to perturb a protein-protein interface in the α-antithrombin dimer; those particular derivatives of 1 were prepared and tested. In the event, most of them significantly accelerated oligomerization of monomeric α-antithrombin, which is metastable in its oligomeric state. This assertion is supported by data from gel electrophoresis (non-denaturing PAGE; thro

SUBMITTER: Xin D 

PROVIDER: S-EPMC4226170 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature