UTMB

Scott Gilbertson, Ph.D.,
Professor

Faculty

Scott Gilbertson, Ph.D.

About the Lab

Our research is centered on the development of new synthetic methods and the utilization of synthetic chemistry for the study of important biological and medical problems. The projects in our laboratory range from the development of new methods in organic synthesis and the total synthesis of biologically important natural products to medicinal chemistry around leads compounds. Doing synthetic chemistry at UTMB provides us with a unique opportunity to test the biological activity of our compounds and make modifications to improve activity or test important biological principles. Some of the projects we are currently working on are:

Development of chemistry for small molecule library synthesis. Combinatorial chemistry is a valuable tool for the discovery of new drug candidates. The ability to synthesize hundreds of compounds for screening is a useful complement to rational drug design. We are developing general approaches for the synthesis of a variety of organic structures. These molecules will then be screened for biological activity often in collaboration with colleagues at UTMB. Some of the biological areas we are developing libraries for are the investigation of anti-viral, anti-cancer, anti-malaria compounds and inhibitors of anthrax edema factor.

Total synthesis and medicinal chemistry of biologically important natural products. We have begun the total synthesis of a number of natural products that possess important biological activity. Our approaches are designed to not only provide the natural product but also to allow for significant modification around a target's basic scaffold. Two systems we are currently working on are Salvinorin A and Dysiherbaine.

Rhodium catalyzed synthesis of medium sized rings. In the area of synthetic methods development, we are working on new reagents to form multiple carbon-carbon bonds in one reaction. One example of such a reaction is a rhodium catalyzed [4+2+2] reaction we have invented. In this case a dieneyne and an alkyne are combined, under rhodium catalysis, to form a new cyclooctatriene. This chemistry is currently being developed for other unsaturated systems and the synthesis of natural products including asteriscanolide.

Peptide based catalysts. Much is known about the three-dimensional structure of peptides. In one project we are using the structural features of these molecules in the de novo design of unnatural enzymes. By designing and building peptides that possess the ability to bind catalytically active transition metals we are developing new types of catalysts. We are taking two approaches to this problem. One method is to synthesize unnatural amino acids, and then by solution phase, solid phase or combinatorial synthesis techniques, build peptides of moderate length. The other route is via the modification of naturally occurring proteins. Proteins that contain unnatural metals have a number of potential uses. In addition to being entirely new types of catalysts, they should be of use as radio-imaging agents, as site-specific DNA cleavage agents and as catalytic enzyme inhibitors.

Interview with Dr. Gilbertson

– by Austin Elam, 2nd year BSCB Student

Dr. Scott Gilbertson began his scientific career at the University of Wisconsin- La Crosse, where he discovered his passion for chemistry. In the following years, he received his Masters Degree from the University of Michigan and performed his Ph.D. research at the University of Chicago with a focus on synthetic chemistry. His research as a NIH post doctoral fellow, also at the University of Chicago, elucidated many chemical mechanisms surrounding plant communication/signaling regarding cell differentiation. Many of his studies also employed nuclear magnetic resonance (NMR) spectroscopy.

"Frankly, I’m amazed at how small the human genome is, compared to other organisms like C. elegans. The advances made in genomics in the last twenty years are staggering."
–Dr. Gilbertson

Dr. Gilbertson came to the University of Texas-Medical Branch (UTMB) from Washington University- St. Louis in 2003. At this time, the biophysical, computational, and structural biology (BSCB) program, was founded but not fully developed. Dr. Gilbertson came to UTMB in order to bring synthetic organic chemistry in concert with people doing medical research. In the BSCB program, there are many people who are trained in biophysics and chemistry; however, having researchers with "solid physical underpinnings with exposure to broad biology in the medical school environment" is what Dr. Gilbertson believes makes the BSCB program unique.

Generally speaking, Dr. Gilbertson has always admired scientists who have evolved over the course of their careers. He cited Dr. Dennis Dougherty, currently the George Grant Hoag Professor of Chemistry at the California Institute of Technology, as a strong example of a scientist who has evolved his ideas and placed fundamental knowledge in a biological context. When asked what specifically motivates him to do research, Dr. Gilbertson enthusiastically commented that "My job is different every day. In science, you can pursue whatever you want to do." He also stated that training the next generation of scientists was an exciting and rewarding experience for him, and that being a scientist was "his hobby as much as his vocation" because he loves his work.

When asked what he thought was the most beautiful observation in all of science, Dr. Gilbertson said, "Frankly, I’m amazed at how small the human genome is, compared to other organisms like C. elegans. The advances made in genomics in the last twenty years are staggering."

Throughout his career Dr. Gilbertson has made several significant scientific observations including the development of systems for using peptide secondary structure or binding of metals to secondary structure to catalyze reactions. Presently, Dr. Gilbertson’s interests span a broad range of research topics in general and synthetic chemistry that include producing ensembles of molecules to build screening libraries for drug development, generation and investigation of amyloid blockers, and ligand design. In the near future, he hopes to make significant progress in the development of each of these areas, and noted that the strength of his lab is its "balance of medical knowledge and fundamental level synthetic chemistry."

Dr. Gilbertson believes that the two qualities most important for graduate students are motivation and knowing your own abilities. He stated that it is vital that students have passion in their research, but commented that the most successful scientists often do well because they focus their research on areas where they excel. Dr. Gilbertson’s message to future students and scientists is to "Do what excites you and have research on your mind at all times."