Adenosine-derived non-phosphate antagonists for P2Y(1) purinoceptors

Novel type antagonists for P2Y(1) adenine nucleotide receptors were synthes ized by coupling of adenosine 5'-OH group with oligo-aspartate chain via a carbonyl linker. All these conjugates (AdoOC(O)Asp(n), n = 1-4) inhibited t he 2MeSADP-stimulated synthesis of inositol phosphates in 1321N1 human astr ocytoma cells stably expressing human P2Y(1) receptors. This inhibitory eff ect followed the rank order AdoOC(O)Asp(2)> AdoOC(O)Asp(3)> AdoOC(O)Asp(1)> AdoOC(O)Asp(4) with antagonistic constant pA(2) = 5.4 for AdoOC(O)Asp(2). Potency of this non-phosphate inhibitor was comparable with the previously known adenosine 3',5'- and 2',5'-bisphosphates. Chemical and biological sta bilities of these novel adenosine derived antagonists of the nucleotide rec eptor provide perspectives of their pharmacological implication. (C) 2000 A cademic Press.