Solution NMR Conformational Analysis of the Potent Equilibrative Sensitive (ES) Nucleoside Transporter Inhibitor,S 6-(4-Nitrobenzyl)mercaptopurine Riboside (NBMPR) |
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| Authors: | John K. Buolamwini Joseph J. Barchi Jr. |
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| Affiliation: | 1. Department of Medicinal Chemistry, and National Center for the Development of Natural Products , Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi , University, MS, 38677;2. Laboratory of Medicinal Chemistry, Division of Basic Sciences , National Cancer Institute, National Institutes of Health , Bethesda, MD, 20892 |
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| Abstract: | ![]()
Abstract High resolution NMR analysis involving one-dimensional (1-D) 1H and nuclear Overhauser (NOE) difference spectroscopy was applied to solutions of NBMPR in DMSO-d 6. Coupling constants were obtained at different temperatures between 285 and 353 K, and used to analyze the rotamer preferences about the C-4′-C-5′ bond. The results revealed a rotamer distribution about the χ tortion angle that favors the high-anti range, a preponderance of the γ+ rotamer (at ～64 %) with respect to the γ torsion angle, and a higher population of the south (S) conformer, which was favored by as little as the 4 % to as much as 31 % over the north (N) conformer as calculated by the program PSEUROT 6.2. The high-anti glycosidic torsion orientation appears to be the major conformational difference between the solution structure of NBMPR determined in this study and the structure previously observed in the solid state. |
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