N59, Hemoglobin S
Nucleic Acid Selection against Hemoglobin S to Prevent the Aggregation of Red Blood Cells in Sickle Cell Anemic Patients
Hemoglobin S differs from normal adult hemoglobin called hemoglobin A only by a single amino acid substitution; a valine replacing a glutamine in the 6th position of the beta chain of globin . This single amino acid substitution causes a genetically inherited disease called sickle cell anemia. This disease results in sickle-shaped red blood cells that deliver less oxygen to the body's tissues. These abnormal cells can also get stuck more easily in small blood vessels, and break into pieces that interrupt healthy blood flow.
Valine is a less polar amino acid than glutamate and thus favors hydrophobic interactions between each strand and its neighboring amino acids such as leucine and Histidine . These types of interactions cause the red blood cells to aggregate and become sickled shaped preventing regular blood flow through capillaries and dramatically decreasing the hemoglobin’s high oxygen-binding affinity .
Selecting an aptamer against hemoglobin S to inhibit the polymerization of red blood cells caused by valine’s reactivity can prevent the sickling of blood cells. Also, it can potentially restore the high oxygen binding affinity of hemoglobin. Although there are drugs such as “Hydroxyurea” that enhance the quality of life of sickle cell anemic patient, this aptamer could be very specific and causing no detrimental side effects.
Specific aim: Synthesis of a specific aptamer that inhibits the aggregation of red blood cells in sickle cell anemic patients.