Structural determinants of A(3) adenosine receptor activation: nucleoside ligands at the agonist/antagonist boundary.

ABSTRACT: Mutagenesis of the human A(3) adenosine receptor (AR) suggested that certain amino acid residues contributed differently to ligand binding and activation processes. Here we demonstrated that various adenosine modifications, including adenine substitution and ribose ring constraints, also contributed differentially to these processes. The ligand effects on cyclic AMP production in intact CHO cells expressing the A(3)AR and in receptor binding were compared. Notably, the simple 2-fluoro group alone or 2-chloro in combination with N(6)-substitution dramatically diminished the efficacy of adenosine derivatives, even converting agonist into antagonist. Other affinity-increasing substitutions, including N(6)-(3-iodobenzyl) 4 and the (Northern)-methanocarba 15, also reduced efficacy, except in co

SUBMITTER: Gao ZG 

PROVIDER: S-EPMC9194716 | biostudies-literature | 2002 Sep

REPOSITORIES: biostudies-literature