The long term objective of this project is to design a new inhibitor for sickle cell hemoglobin that may lead to an alternative treatment for suppressing the symptoms of the sickle cell disease. Specifically, beginning with a number of potent inhibitors, locate the binding site(s) on the sickle hemoglobin, analyze the interactions, and identify how the polymerization can be disrupted. Molecular docking of the ligands in the most probable binding sites and evaluating the energies will allow a """"""""score"""""""" to be given for each site, and allow a ranking of each site. Locating a crucial binding site for an inhibitor will lead to the screening of large databases for other potential candidates. Many of the binding sites appear to be located near the lateral acceptor pocket. However, the axial contact sites within a strand will also be examined for determining the role the axial region plays in stabilizing the polymer fiber. Electrostatics, solvation models, and molecular docking calculations will be used to accomplish this task.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32HL010231-01
Application #
6012748
Study Section
Metallobiochemistry Study Section (BMT)
Project Start
1999-12-15
Project End
Budget Start
1999-12-15
Budget End
2000-12-14
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Illinois at Chicago
Department
Nutrition
Type
Schools of Allied Health Profes
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612
Park, Soobong; Hayes, Brittany L; Marankan, Fatima et al. (2003) Regioselective covalent modification of hemoglobin in search of antisickling agents. J Med Chem 46:936-53