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Biomedical subjects

R H Sarma

Publications and source records attributed to R H Sarma.

At least 73 records · Page 4Linked to original sources
PubMed1975

Interrelation between glycosidic torsion, sugar pucker, and backbone conformation in 5'-beta-nucleotides. A 1H and 31P fast Fourier transform nuclear magnetic resonance investigation of the conformation of 8-aza-5'-beta-adenosine monophosphate and 8-aza-5'-beta-guanosine monophosphate.

Hydrogen-1 and phosphorus-31 nuclear magnetic resonance spectra of 5'-AMP, 5'-GMP, 8-aza-5'-GMP, adenosine, 8-aza-adenosine, and guanosine were obtained at biological pH values at a concentration sufficiently low to obtain information regarding their intramolecular solution conformation. The spectra were analyzed by computer simulation. It is shown that all of the above nucleosides and nucleotides have a flexible molecular framework in aqueous solution, 5'-AMP and 5'-GMP showing preference for anti(2-E in equilibrium 3-E)gg-g'g' conformations and the 8-aza analogs showing preference for (syn in equilibrium anti)-(2E in equilibrium 3-E) - g/t-g'g' conformations. In addition, aza substitution causes increase in 3-E sugar populations and in the populations of g'/t' conformers. It is argued that in the 8-aza analogs repulsive electrostatic interactions would prevail between --N (see article) at the 8 position and the negatively charged phosphate group, if the molecule existed in the anti-gg orientation. Such electrostatic repulsions can be relieved by rotating the C(4')--C(5') bond from gg to g/t orientations as well as by torsional variation about the glycosidic linkage from anti to syn conformation. Rotation from anti to syn orientation, for steric and electrostatic reasons, necessitates a simultaneous rotation about the C(4')--C(5') bond from gg to g/t conformation. The observation that the 8-aza substitution in 5'-beta-purine nucleotides cause a depopulation of gg and anti conformers with corresponding increase in the population of g/t and syn orientation seems to support the above thesis. The finding that rotational variation about a bond such as C(4')--C(5') is accompanied by torsional variation about C(5')--O(5') and the glycosidic bonds, as well as changes in the endocyclic torsion angles of the ribose moiety, gives important insight into the engineering of nucleic acid components: even though they in general prefer certain conformations, there is enough flexibility present in their molecular framework, that the entire system can undergo conformational adjustment in response to a perturbation. A conformational basis for the antileukemic effects of 8-aza purines is proposed.

Adenosine↗
PubMed1975

The aqueous solution conformation of tubercidin and tubercidin 5'-phosphate.

The backbone of tubercidin and tubercidin 5'-phosphate in aqueous solution has a flexible molecular framework with preference for 2E-gg and 2E-gg-g'g' conformations, respectively. The glycosyl bond is unusually flexible and no definite preference for either anti or syn conformation could be detected. It is proposed that the incorporation of tubercidin 5'-phosphate into nucleic acids will disrupt the polymeric structure because of the high accessibility of syn conformation, and this might be related to the reported inhibition of nucleic acid and protein synthesis.

Chemical Phenomena↗