BIOCHEMICAL AND PHARMACOLOGICAL CHARACTERIZATION OF PERIODATE-OXIDIZED ADENOSINE-ANALOGS AT ADENOSINE A(1) RECEPTORS

Periodate oxidation of eight N-6-substituted adenosine derivatives was performed with the aim of oxidizing the vicinal 2' and 3' hydroxyl gr oups of the ribose moiety. A thermodynamical and pharmacological chara cterization of the products of this transformation allowed us to verif y that oxidized adenosine analogues act as agonists at adenosine A(1) receptors. The dependence of their association constants on temperatur e indicates that their binding is entropy driven, a feature typical of adenosine A1( )receptor agonists; moreover all synthesized compounds were able to fully inhibit the forskolin induced c-AMP accumulation in rat isolated adipocytes. This is the first report suggesting that the presence of an intact ribose moiety is not necessary for agonistic ac tivity at adenosine A(1) receptor. In fact periodate oxidation of the ribose moiety yields a dialdehyde and it is recognized that nucleoside dialdehydes are complex equilibrium mixtures of cyclic and acyclic hy drates and hemiacetals.