Periodate oxidation of eight N-6-substituted adenosine derivatives was performed with the aim of oxidizing the vicinal 2' and 3' hydroxyl groups of the ribose moiety. A thermodynamical and pharmacological characterization of the products of this transformation allowed us to verify that oxidized adenosine analogues act as agonists at adenosine A(1) receptors. The dependence of their association constants on temperature 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 activity 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 hydrates and hemiacetals.
BIOCHEMICAL AND PHARMACOLOGICAL CHARACTERIZATION OF PERIODATE-OXIDIZED ADENOSINE-ANALOGS AT ADENOSINE A(1) RECEPTORS
MARTINI, CLAUDIA;CHIELLINI, GRAZIA;LUCACCHINI, ANTONIO
1995-01-01
Abstract
Periodate oxidation of eight N-6-substituted adenosine derivatives was performed with the aim of oxidizing the vicinal 2' and 3' hydroxyl groups of the ribose moiety. A thermodynamical and pharmacological characterization of the products of this transformation allowed us to verify that oxidized adenosine analogues act as agonists at adenosine A(1) receptors. The dependence of their association constants on temperature 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 activity 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 hydrates and hemiacetals.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
