Designing photoaffinity tool compounds for the investigation of the DENV NS2B-NS3 protease allosteric binding pocket.

ABSTRACT: Dengue virus (DENV) infection still lacks specific antiviral therapy, making the NS2B-NS3 protease an attractive target for drug development. However, allosteric inhibitors that bind to a site other than the active site still need to be better understood. In this study, we designed and synthesised tool compounds for photoaffinity labelling (PAL) to investigate the binding site of allosteric inhibitors on the DENV protease. These tool compounds contained an affinity moiety, a photoreactive group, and a reporter tag for detection. Upon irradiation, the photoreactive group formed a covalent bond with the protease, allowing for binding site identification. SDS-PAGE-based assays confirmed the qualitative binding of the designed inhibitors to the allosteric pocket, and pull-down experiments vali

SUBMITTER: Maus H 

PROVIDER: S-EPMC10650954 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature