The Baylor CPRIT Synthesis and Drug-Lead Discovery Laboratory will focus on the devolpment and application of chemo- and site-selective methods for the derivatization of biologically and pharmacologically important natural products and other bioactive small molecules and the high throughput optimization of synthetic transformations. Given that derivatization for structure-activity relationship (SAR) studies and reaction optimization play fundemental roles in drug discovery, it is envisioned that the CPRIT Laboratory’s high throughput capabilities will serve to drive collaboration and discovery among an interdisciplinary group of researchers extending beyond Baylor to both the national and international levels. Indeed, several ongoing local, state, national and international collaborations are underway. This Departmental Laboratory will provide assistance with reaction optimization and isolation, purification, and structural elucidation of the derived products. An additional primary function will be to develop collaborations with researchers who can provide purified natural products (ideal) or semi-purified extracts exhibiting novel and potent bioactivity. The role of the Baylor CPRIT Lab in these collaborative effots will be to provide chemo- and site selective derivatizations of the natural product designed to facilitate preliminary SAR studies. Typically these studies will be the first step in enabling the synthesis of bioactive cellular probes (e.g. biotin, fluorophore, radiolabelled conjugates) that can, in turn, be employed in cellular localization studies and cellular receptor isolation. These latter studies are critical to elucidating the mechanism of action of the bioactive substance and providing information that can also be useful for de novo synthesis of simplified equipotent derivatives of the natural product which in turn serve as useful drug-leads. Data generated from these collaborations will serve as critical and necessary Preliminary Results for submission of research grants to futher support the interdisciplinary collaborative research efforts of the CPRIT Lab. Thus, this laboratory fosters synergy among a diverse group of researchers who share a common interest in harvesting the enduring potential of bioactive natural products and derivatives as drug leads. This is accomplished by providing access to a suite of chemo- and site-selective derivatization reactions, high throughput reaction optimization equipment, both analytical and semi-preparative purification, and characterization tools all guieded by a group of established investigators with track records in the synthesis and biology of complex natural products.
Missions and Goals Jed Ostrom