NBMPR-BINDING SITE OF THE HUMAN ES ADENOSINE TRANSPORTER

描述

DESCRIPTION (Adapted from applicant's abstract) This is a Mentored Minority Faculty Development Award Proposal designed to provide the necessary mentoring and research activities necessary to enable the PI achieve his career goals of becoming an established independent academic investigator in the cardiovascular research and drug discovery field. The proposal responds to the timely initiative of the National Heart Lung and Blood Institute to prepare underrepresented minorities scientists as independent investigators. Cardiovascular disease is the number cause of death among the American population, afflicting 1.5 million Americans with a new or recurrent heart attack, and killing over 980,000 people every year. Minorities especially African-Americans are disproportionately affected. There is definitely a need more minority researchers in the cardiovascular field especially in Mississippi, which houses a large African-American Population. This proposal seeks to provide intensive mentoring and research training for the PI who is a minority assistant professor at a predominantly white higher institution, the University of Mississippi. The overall career goals of the candidate are to acquire research capabilities in areas of experimental analysis of protein- ligand complex interactions at the molecular level using photo labeling, affinity purification and use them to structurally characterize the interaction of inhibitors with the es adenosine (nucleoside) transporter to obtain insights that will be used to design and develop more specific and potent adenosine transport inhibitors as potential cardioprotective and neuroprotective drugs. Adenosine is a physiological nucleoside that is released in ischemic conditions such as a heart attack or stroke to protect tissue injury. However, its rapid uptake by nucleoside transporters abrogates this protective action. Nucleoside transport inhibitors block adenosine uptake by cells, and therefore enhance its extracellular protective effects. The inhibition of adenosine transport has therapeutic potential in heart disease and stroke that has yet to be tapped by he design and discovery of inhibitors with the requisite pharmacological profiles. Designed compounds will be synthesized and tested as es transporter ligands and adenosine transport inhibitors by flow cytometry and radioisotope methods. The candidate will receive mentorship by established well-accomplished investigators, the primary and secondary sponsors, and a cadre of four senior faculty serving on the candidates advisory committee. Ancillary course work in advanced protein techniques, mass spectrometry and experimental design, as well as American Chemical Society techniques workshops, and our research office workshops. Biweekly research progress meetings will be held with sponsors and committee members.