Fluorination Influences the Bioisostery of Myo-Inositol Pyrophosphate Analogs.

ABSTRACT: Inositol pyrophosphates (PP-IPs) are densely phosphorylated messenger molecules involved in numerous biological processes. PP-IPs contain one or two pyrophosphate group(s) attached to a phosphorylated myo-inositol ring. 5PP-IP₅ is the most abundant PP-IP in human cells. To investigate the function and regulation by PP-IPs in biological contexts, metabolically stable analogs have been developed. Here, we report the synthesis of a new fluorinated phosphoramidite reagent and its application for the synthesis of a difluoromethylene bisphosphonate analog of 5PP-IP₅ . Subsequently, the properties of all currently reported analogs were benchmarked using a number of biophysical and biochemical methods, including co-crystallization, ITC, kinase activity assays and chromatograp

SUBMITTER: Hostachy S 

PROVIDER: S-EPMC7615343 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature