Laboratory of Bioorganic Chemistry - (LBC)
Research carried out by the Laboratory of Bioorganic Chemistry is designed to explore problems at the interface of chemistry and biology. Projects include studies on the mechanisms of interaction of pharmacologically active substances with biological systems, including systems relevant to diabetes, cancer, tuberculosis, AIDS, Parkinsonism, Alzheimer's disease and chronic pain. One goal of this research is to discover and develop new chemical agents including synthetic molecules and natural products as tools for the study of membrane and cytosol functions of cells. Mechanisms of action or metabolism of such agents and their potential use as therapeutics are examined. An integral part of this research involves the development and application of modern techniques of bioorganic chemistry for the synthesis, separation, and spectral and biological investigation of new chemical agents, including bioactive natural products. In addition, experiments in nuclear magnetic resonance spectroscopy and mass spectrometry are designed, developed, and carried out to elucidate structures of both small and macro-molecules. One area of research involves the use of covalent DNA adducts derived from metabolites of environmental carcinogens as probes of enzyme function. New synthetic methods have been developed for site- and stereospecific incorporation of these adducts into oligonucleotides. These oligonucleotides are used to map the catalytic and recognition sites of enzymes such as DNA polymerases, helicases, integrases, and topoisomerases. New approaches to drug delivery, affinity labeling, enzyme catalysis, and receptor activation and new concepts of drug design are investigated. Modern techniques in molecular biology are used to study mechanisms of cell surface receptor activation and signal transduction, particularly with respect to adenosine, ATP, adrenergic, nicotinic and muscarinic receptors and the ion channels and second messengers subserving such receptors. Trans-genic mice are developed for in vivo investigation. Receptor mutagenesis studies in conjunction with homology modeling have elucidated the requirements for molecular recognition in the ligand binding site and G protein interface and structural aspects of receptor activation.
Page last updated: February 12, 2009
