4-Alkyloxyimino-cytosine nucleotides: tethering approaches to molecular probes for the P2Y₆ receptor.

ABSTRACT: 4-Alkyloxyimino derivatives of pyrimidine nucleotides display high potency as agonists of certain G protein-coupled P2Y receptors (P2YRs). In an effort to functionalize a P2Y₆R agonist for fluorescent labeling, we probed two positions (N⁴ and γ-phosphate of cytidine derivatives) with various functional groups, including alkynes for click chemistry. Functionalization of extended imino substituents at the 4 position of the pyrimidine nucleobase of CDP preserved P2Y₆R potency generally better than γ-phosphoester formation in CTP derivatives. Fluorescent Alexa Fluor 488 conjugate 16 activated the human P2Y₆R expressed in 1321N1 human astrocytoma cells with an EC₅₀ of 9 nM, and exhibited high selectivity for this receptor over

SUBMITTER: Jayasekara PS 

PROVIDER: S-EPMC4493932 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature