Stable-isotope labeled nucleosides or nucleotides were identified as crucial for further advances in NMR study of structures and dynamics of DNA's and RNA's. Investigators in this field have suggested nucleosides/- tides 13C-labeled at C-l',3',5' as most useful and cost-effective. This Phase I project aims to synthesize 4-hydroxy-(5R)- hydroxymethyltetraltydrofuran-2-one-2,4 (hydroxymethyl)-13C3, or compound 9, as the key intermediate using a new labeled precursor recently developed in our lab. Phase II will pursue the conversion of compound 9 into labeled dA dG, dC and T, and A, G, C, and U. The nucleosides will then be further elaborated into the corresponding deoxyribophosphoramidites or ribonucleoside triphosphates, each labeled with 99% carbon-l3 at C-l',3,'5' and ready to be used for the preparation of labeled DNA's or RNA's.
Direct commercial potential appears relatively modest due to limited applications to research. However, the labeled nucleosides/-tides may lead to breakthroughs in structural study of DNA's/RNA's which, in turn, may allow further advances in the areas of molecular basis of diseases and rational drug-design.
