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Synthesis and P2Y receptor activity of nucleoside 5'-phosphonate derivatives.

ABSTRACT: Ribose-based nucleoside 5'-diphosphates and triphosphates and related nucleotides were compared in their potency at the P2Y receptors with the corresponding nucleoside 5'-phosphonate derivatives. Phosphonate derivatives of UTP and ATP activated the P2Y(2) receptor but were inactive or weakly active at P2Y(4) receptor. Uridine 5'-(diphospho)phosphonate was approximately as potent at the P2Y(2) receptor as at the UDP-activated P2Y(6) receptor. These results suggest that removal of the 5'-oxygen atom from nucleotide agonist derivatives reduces but does not prevent interaction with the P2Y(2) receptor. Uridine 5'-(phospho)phosphonate as well as the 5'-methylenephosphonate equivalent of UMP were inactive at the P2Y(4) receptor and exhibited maximal effects at the P2Y(2) receptor that were 50% of that of UTP suggesting novel action of these analogues.

SUBMITTER: Cosyn L

PROVIDER: S-EPMC2721324 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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Synthesis and P2Y receptor activity of nucleoside 5'-phosphonate derivatives.

Cosyn Liesbet L Van Calenbergh Serge S Joshi Bhalchandra V BV Ko Hyojin H Carter Rhonda L RL Kendall Harden T T Jacobson Kenneth A KA

Bioorganic & medicinal chemistry letters 20090414 11

Ribose-based nucleoside 5'-diphosphates and triphosphates and related nucleotides were compared in their potency at the P2Y receptors with the corresponding nucleoside 5'-phosphonate derivatives. Phosphonate derivatives of UTP and ATP activated the P2Y(2) receptor but were inactive or weakly active at P2Y(4) receptor. Uridine 5'-(diphospho)phosphonate was approximately as potent at the P2Y(2) receptor as at the UDP-activated P2Y(6) receptor. These results suggest that removal of the 5'-oxygen at ...[more]

PMID: 19419868

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