Chimeras Derived from a P2Y₁₄ Receptor Antagonist and UDP-Sugar Agonists for Potential Treatment of Inflammation.

ABSTRACT: Tethered glycoconjugates of a naphthalene- and piperidine-containing antagonist of the P2Y₁₄ receptor (PPTN) were synthesized, and their nM receptor binding affinity was determined using a fluorescent tracer in hP2Y₁₄R-expressing whole CHO cells. The rationale for preparing mono- and disaccharide conjugates of the antagonists was to explore the receptor binding site, which we know recognizes a glucose moiety on the native agonist (UDP-glucose), as well as enhance aqueous solubility and pharmacokinetics, including kidney excretion to potentially counteract sterile inflammation. Glycoconjugates with varied linker length, including PEG chains, were compared in hP2Y₁₄R binding, suggesting that an optimal affinity (IC₅₀, nM) in the piperidine series w

SUBMITTER: Wen Z 

PROVIDER: S-EPMC11480895 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature