Synthesis of an α-phosphono-α,α-difluoroacetamide analogue of the diphosphoinositol pentakisphosphate 5-InsP₇.

ABSTRACT: Diphosphoinositol phosphates (PP-InsPs) are an evolutionarily ancient group of signalling molecules that are essential to cellular and organismal homeostasis. As the detailed mechanisms of PP-InsP signalling begin to emerge, synthetic analogues of PP-InsPs containing stabilised mimics of the labile diphosphate group can provide valuable investigational tools. We synthesised 5-PCF₂Am-InsP₅ (1), a novel fluorinated phosphonate analogue of 5-PP-InsP₅, and obtained an X-ray crystal structure of 1 in complex with diphosphoinositol pentakisphosphate kinase 2 (PPIP5K2). 5-PCF₂Am-InsP₅ binds to the kinase domain of PPIP5K2 in a similar orientation to that of the natural substrate 5-PP-InsP₅ and the PCF₂Am st

SUBMITTER: Riley AM 

PROVIDER: S-EPMC6657673 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature