Area of Doctoral Study: Chemistry
Undergraduate Institution: Morgan State University
Research Advisor: Ramachandra S. Hosmane, Ph.D.
Current: Chemist, Pharmaceutical Ploymer Company, Ontario, California
Description of Research
The overall aim of my project is to develop a physiologically compatible substitute for human blood for emergency transfusions. The need for such a blood alternative is becoming increasingly pressing in view of the scarcity of blood, especially when rare types are needed, the possible transmission of diseases associated with blood transfusion such as AIDS and hepatitis, the limitations on storage stability of intact blood, the necessity for blood typing before transfusion, and not to mention other reasons, for example, the reluctance to accept an alien blood for transfusion on religious grounds. Efforts to develop alternatives to blood as an oxygen carrier date back well over half a century. While a number of other alternatives have been explored over the years, the use of cell-free hemoglobin for an oxygen-carrying resuscitation fluid has excellent prospects since (a) hemoglobin solutions are completely metabolizable and are well tolerated by the body, and (b) hemoglobin is available in virtually unlimited amounts and is relatively inexpensive, (c) hemoglobin is fully saturated with oxygen under ambient conditions, has oncotic activity, and exhibits cooperative oxygen binding behavior. However, there are two major problems associated with using cell-free hemoglobin for transfusions. First, the retention time of cell-free hemoglobin in circulation after infusion is very short, and most of the infused hemoglobin is rapidly filtered and eliminated by kidneys; second, cell-free hemoglobin have too high oxygen affinity that prevents them from adequately unloading the oxygen acquired from lungs to tissues. Both of these problems have their roots in a small organic molecule called 2,3-diphosphoglycerate (DPG) which is conspicuously absent in cell-free hemoglobin, but is known to be an essential co-factor in intact red blood cells. Covalently cross-linking the hemoglobin subunits with a DPG mimic is believed to alleviate both of the mentioned problems. To this end, we are involved in computer-aided design and chemical synthesis of novel bifunctional organic reagents (BOR’s) to cross-link hemoglobin. The modified cell-free hemoglobin are to be used as substitutes for blood as oxygen carriers in emergency transfusions. My specific research project involves synthesis, hemoglobin cross-linking, and biochemical studies involving one such BOR called the m-BCCEP