Application of NMR to solve structural problems continues to be a major interest in the past year. In collaboration with Dr. J. Daly's group (NIDDK), structures of a number of biomolucules isolated from nature sources are successfully determined. These include 1) a new diterpene diacetate from the Madagascan termite, Nasutitermes canaliculatus, 2) two nineteen-carbon alkaloids (one as cis- and the other as trans-fused 2,5-disubstituted decahydroquinolines with C-2 and C-8a hydrogens cis in both DHQa) isolated from skin extracts of dendrobatid frogs, and 3) a major alkaloid, a 1,4-disubstitued quinolizidine, isolated from skin of a mantelline frog (mantella). Also, in collaboration with Dr. Elise Kohn (NCI), a metabolite of CAI (a calcium influx inhibitor and cytostatic agent used in phase I trial for patients with refractory cancer) was identified and characterized. NMR and mass spectrometry analysis of the purified compound indicated that it is a 3,5-dichloro-4(p-chlorobenzoyl)-benzoic acid. Using 2D NMR spectroscopy and molecular modelling we have investigated solution structures of oligonucleotide duplexes modified at N-6 of the central deoxyadenosine residue by addition to C-10 isomeric 7,8-diol 9,10-epoxide metabolites of benzo[a]pyrene (BPDEs) (in collaboration with Dr. D. M. Jerina~s group). The hydrocarbon in all dA adducts investigated to date is intercalated into the DNA helix at the 3'-end of the modified dA when the absolute configuration at C-10 of the hydrocarbon is S and at the 5'-end when the absolute configuration is R. This is in contrast to the dG adducts in which the hydrocarbon lies outside at the minor groove and orients toward the 3'-end of the modified dG when the absolute configuration is R and toward the 5'-end when the absolute configuration is S.
