Sickle cell disease is a genetic disorder affecting the hemoglobin within red blood cells. A point mutation in the gene coding for the �-subunit of hemoglobin allows the mutant chain to interact with a hydrophobic pocket of another hemoglobin in a deoxygenated environment, causing polymerization of the proteins. This creates the characteristic sickle-shape of the diseased blood cells that can clog capillaries, leading to tissue damage and cell death. Currently, there are limited options for those affected with sickle cell disease. The research to be presented is focused on discovering peptides that can interact with the mutated hemoglobin and prevent aggregation. The synthesis of peptides on solid support allows for the construction of diverse libraries, which can readily be screened for protein binding. Phage display can be utilized to discover tight-binding ligands. Thus far, we have discovered several possible ligands and are currently characterizing their binding interactions to determine if they are capable of inhibiting hemoglobin polymerization. Additionally, peptide derivatives with better bioavailability and binding affinity are also being investigated. This work represents a novel approach for the discovery of therapeutics for this debilitating disorder.

Discovery of novel peptidic ligands for sickle cell hemoglobin

248th National Meeting (2014)

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