Purine 3′:5′-cyclic nucleotides with the nucleobase in asynorientation: cAMP, cGMP and cIMP

Abstract

Purine 3′:5′-cyclic nucleotides are very well known for their role as the secondary messengers in hormone action and cellular signal transduction. Nonetheless, their solid-state conformational details still require investigation. Five crystals containing purine 3′:5′-cyclic nucleotides have been obtained and structurally characterized, namely adenosine 3′:5′-cyclic phosphate dihydrate, C10H12N5O6P·2H2O or cAMP·2H2O, (I), adenosine 3′:5′-cyclic phosphate 0.3-hydrate, C10H12N5O6P·0.3H2O or cAMP·0.3H2O, (II), guanosine 3′:5′-cyclic phosphate pentahydrate, C10H12N5O7P·5H2O or cGMP·5H2O, (III), sodium guanosine 3′:5′-cyclic phosphate tetrahydrate, Na+·C10H11N5O7P−·4H2O or Na(cGMP)·4H2O, (IV), and sodium inosine 3′:5′-cyclic phosphate tetrahydrate, Na+·C10H10N4O7P−·4H2O or Na(cIMP)·4H2O, (V). Most of the cyclic nucleotide zwitterions/anions [two from four cAMP present in total in (I) and (II), cGMP in (III), cGMP−in (IV) and cIMP−in (V)] aresynconformers about the N-glycosidic bond, and this nucleobase arrangement is accompanied by Crib—H...Npurhydrogen bonds (rib = ribose and pur = purine). The base orientation is tuned by the ribose pucker. An analysis of data obtained from the Cambridge Structural Database made in the context ofsyn–anticonformational preferences has revealed that among thesynconformers of various purine nucleotides, cyclic nucleotides and dinucleotides predominate significantly. The interactions stabilizing thesynconformation have been indicated. The inter-nucleotide contacts in (I)–(V) have been systematized in terms of the chemical groups involved. All five structures display three-dimensional hydrogen-bonded networks.