Gary A. Sulikowski
Stevenson Professor of Chemistry & Professor of Pharmacology
Director, Vanderbilt Institute of Chemical Biology
Dr. Sulikowski is not currently accepting graduate students.
Gary Sulikowski received a BS in chemistry from Wayne State University and a PhD in organic chemistry from the University of Pennsylvania. He was an Amer¬ican Cancer Society postdoctoral fellow at Yale University. His first facul¬ty appointment was in the Department of Chemistry at Texas A&M Univer¬sity in 1991 and joined the Vanderbilt Chemistry Department and Institute of Chemical Biology in 2004. He is the faculty Director of the Institute of Chemical Biology Chemical Synthesis core, Stevenson Professor of Chem¬istry and Professor of Pharmacology. Sulikowski’s research interests are on the design and development of chemical syntheses of complex molecules, specifically bioactive natural products and molecular probes. Over time his interests have expanded to the chemical synthesis of molecular tools with application in biological research and therapeutic lead development. He has published over 130 research publications and co-authored 12 patents.
Biology and chemistry of natural products. Natural products are among the most structurally complex and privileged of the bioactive small molecules. Analysis of the sources of small molecule drugs approved between 1981 and 2006 indicates that over half of the new chemical entities declared in this timeframe were natural products or derived from natural products. However, from the perspective of medicinal chemistry, the complex molecular architecture of natural products continues to pose a significant challenge to access not only quantities of the parent structure but also analogs to establish structure-activity relationships (SAR). In addition to utilizing our skills in chemical synthesis to access and modify natural products we also attempt to harness the biosynthetic machinery to access complex natural products, sometimes in collaboration with groups with expertise the genetic modification of biosynthetic pathways. We were the first group to identify the biosynthesis of the complex nonadrides CP-225,917 and CP-263,114 and study the development of this biosynthetic dimerization in the lab. More recently, working with the Bachmann group we have developed fluorescent derivatives the cell selective cytotoxic agent apoptolidin and demonstrated its localization in the mitochondria. We are also one of two groups in the world that developed a chemical synthesis of the microbial thiol bacillithiol, now being used by investigators worldwide.
Chemical probes and pre-clinical lead development. Phenotypic and functional screens of compound libraries are currently being used by a variety of biomedical investigators in Cell and Developmental Biology, Microbiology and Immunology and Pharmacology. We provide chemistry support in lead development and target identification studies. In some cases we have optimized lead potency and metabolic compound properties allowing animal studies to provide preliminary validation of new targets for therapeutic development.