Rawle I. Hollingsworth Research Interests
Development of synthetic strategies for compounds in medicinal chemistry
One major area of our research program is the development of synthetic strategies for compounds of interest in medicinal chemistry. We are especially interested in the synthesis of compounds with dense functionality containing one or more chiral centers. Our main approach in this endeavor is the utilization of chemical functionality from the vast structural reservoirs of carbohydrate materials found naturally. Using this approach we have developed synthetic routes to a variety of compound classes that are of interest in the design, development and manufacture of drugs used in therapeutic applications ranging from cholesterol lowering through cancer, infectious diseases, autoimmune disorders and diabetes. We have ongoing programs in the development of new drug candidates using structure-based design guided by screening programs targeting several enzymes especially those involved in carbohydrate, glycoprotein, glycolipid and nucleic acid processing. Cancer, infectious diseases, amyloid disorders (e.g Alzheimer’s and diabetes) are included in this focus.
Biomaterial Design
We also have an ongoing program in the area of biomaterial design. This is targeted at materials for uses such as drug delivery, implants and artificial tissue as well as for several environmental, sensor and diagnostic applications. We have developed several molecular platforms to facilitate the preparation of compounds with a wide spread of physical properties ranging from gels to resins to sheets to vesicles to lamellar systems aimed at a wide spectrum of end uses.
Structural attributes that regulate behavior and properties of biomolecules
The other major research interests of our laboratory are all focused on trying to understand what structural attributes regulate the behavior and properties of biomolecules in the context of living systems. We are especially interested in large ensemble systems, especially biomembranes. One major goal is to determine how biomembranes control or influence the behavior of macromolecules such as proteins and nucleic acids. The studies we are engaged in involve a large spectrum of biochemical, chemical, and physical methods. These include organic synthesis and a large variety of spectroscopic and computational tools, especially NMR and IR spectroscopy and molecular structure calculation, as well as the analysis and simulation of molecular dynamics. Our work involves studies on molecular recognition using model systems such as the Rhizobium/legume symbiosis. Another area of study is the adaptive processes bacteria use in going from one set of environmental parameters to another. In both cases, the importance of membrane chemistry is stressed.