About the Lab
The Laboratory of Bioorganic Chemistry (LBC) explores biomedical problems at the interface of chemistry and biology. Founded by the late John Daly in 1978, LBC has a rich history of chemical research that includes organic synthesis, medicinal chemistry, natural products chemistry, structural biology and pharmacology.
Scientists in the LBC work on diverse topics in bioorganic chemistry that include:
- development of conjugate vaccines from synthetic carbohydrate antigens
- the use of synthetic organic chemistry to create new molecules with unique biological activities
- pharmacology and drug discovery of agonists or antagonists of membrane receptors
- structural characterization of G-protein coupled receptors
- discovery and development of biologically active natural products
- engineering of proteins and oligomers for diagnostics, therapeutics and vaccines
- structural and biophysical characterization of non-human carbohydrate-binding proteins
Projects include studies on the mechanisms of interaction between pharmacologically active substances and biological systems. These include biological systems relevant to diabetes, cancer, inflammatory diseases, tuberculosis, HIV/AIDS, Parkinson’s disease, Alzheimer's disease, and chronic pain. One of the lab’s goals is to discover and develop diverse small molecules and biologics, encompassing synthetic molecules, natural products and oligomers as tools for the study of membrane and intracellular processes. Researchers examine the mechanisms of action or metabolism of such agents and their potential use as therapeutics. An integral part of this research involves the development and application of modern techniques in organic, medicinal and analytical chemistry. Lab scientists use these techniques to synthesize, separate, and investigate the spectral and biological characteristics of new chemical agents, including bioactive natural products.
In addition, scientists design, develop, and carry out experiments in nuclear magnetic resonance spectroscopy and mass spectrometry to elucidate structures of both small molecules and macromolecules. One area of research involves the use of custom-designed peptide-nucleic acids as probes of protein and nucleic acid interactions. Utilizing the synthesis of complex carbohydrates, researchers have developed synthetic vaccines for application to infectious diseases. They also investigate new approaches to drug delivery, affinity labeling, enzyme catalysis, and receptor activation and new concepts of drug design.
Finally, lab scientists use modern techniques in molecular biology to study mechanisms of cell surface receptor activation and signal transduction. Of particular interest are adenosine, ATP, adrenergic, nicotinic, and muscarinic receptors and the ion channels and second messengers subserving such receptors. Researchers develop transgenic mice for in vivo investigations. Receptor mutagenesis studies and homology modeling—in conjunction with the use of recently determined X-ray crystallographic structures—have elucidated the requirements for molecular recognition in the ligand binding site and G protein interface, as well as structural aspects of receptor activation. Lab scientists are using these insights to design new drug analogues with superior pharmacological properties and potentially fewer side effects.