Our research has two major goals. One involves discovery of new organic chemistry of nucleosides, nucleotides, and related biomolecules, which are at the core of genetic and biochemical genetic processes. We devise new reactions and stereochemically defined transformations with these nucleic acid components and analogues, and apply BYU’s state-of-the-art instrumentation to studies on structural properties. NMR and X-ray crystallography reveal stereochemical, stereoelectronic, and conformational effects in the sugar-base units of target compounds.

     The other goal is discovery of new biochemical/molecular biological tool molecules and useful medicinal agents. Our pioneering syntheses of purine 2’,3’-dideoxynucleosides helped provide access to the dideoxynucleoside triphosphates that are used routinely in gene sequencing. We developed the first synthesis of 2’,3’-dideoxyadenosine and from it the anti-HIV drug DDI (didanosine). We pursued collaborative studies with analogues that led to development of the first effective drug for treatment of hepatitis B. This work resulted in our sharing the 1998 Prix Galien Canada Research Award. We also were the first to prepare 2-chloro-2’-deoxyadenosine (cladribine), a drug effective against hairy-cell leukemia and other cancer and related diseases. We recently developed improved syntheses of cladribine, which have resulted in the filing of new patent applications.

     Another area of investigation in our laboratory involves invention of mechanism-based inhibitors of enzymes vital to cancer cell and/or virus proliferation. We design nucleoside analogues with groups that are chemically activated in the initial steps of enzyme mechanisms. Spontaneous reactions within the active site, and/or after release of a reactive species, cause inactivation of the enzyme. Such compounds also have contributed to elucidation of new aspects of the mechanisms of enzyme-catalyzed reactions. Certain mechanism-based inactivators of crucial enzymes have demonstrated potent pharmacological effects, and clinical drugs have been developed.

     Our laboratory is focused on the design and synthesis of new agents. We have exciting collaborations with leading biologists throughout the world for enzyme inactivation studies and biomedical applications. Graduate students and postdoctoral fellows choose projects in harmony with their interests, usually with both chemical and biomolecular aspects. Participation in the laboratories of our collaborators also provides an opportunity for direct biological experimentation.