A major mission of this group involves the basic research and service functions of NMR instrumentation providing to NIDDK scientists of the Laboratory of Bioorganic Chemistry, Laboratory of Medicinal Chemistry, other NIH laboratories and, to a limited extent, to scientists of other institutes. The two high field (500 MHz and 600 MHz) instruments are now in full operation and have been widely used by investigators from different laboratories. Collaborative projects that use these two high field instruments include 1) structural elucidation of new alkaloids isolated from frog skin (in collaboration with Dr. John Daly?s group), 2) conformational studies of structurally altered DNA resulting from chemical modification by diolepoxides fromed from known chemical carcinogens, such as benzo[a]pyrene (BaP) (in collaboration with Dr. Donald Jerina?s group) and 3) conformational studies of agonist and antagonist of nucleotide P2Y receptors. A number of methanocarba analogues, which have a fused cyclopropane ring at the C4? and C5? of a 5 member-ring moiety of the carbocyclic neucleoside, are known to enhance potency toward many P2Y receptors. Preference of a (N)-conformation over a (S)-conformation at the 5 member-ring moiety is suggested as a major cause for the potency enhancement. Our NMR results prove that these methanocarba analogues adopt predominantly (>93%) an N-state (C2?-exo) conformation.