Synthesis and evaluation of stable substrate analogs as potential modulators of cyclodiphosphate synthase IspF

Abstract

Stable IspF substrate analogs were synthesized. In the presence of substrate analogs, the E. coli IspF–MEP complex shows activities distinct from IspF, and bisphosphonates (BP) behave differently than their diphosphate (DP) counterparts. Bisphosphonate analogs activate and/or stabilize IspF, and only the closest structural substrate analog weakly inhibits the IspF–MEP complex.