Sickle cell disease is a genetic disorder that affects the hemoglobin within red blood cells. A point mutation in the gene coding for the β-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. A novel proline-rich peptide ligand, ZSF39, was identified through a phage display against deoxygenated sickle cell hemoglobin. A combinatorial peptide library based on the structure of ZSF39 was synthesized and screened for binding affinity using an ELISA. A tightly binding peptide, LHSl, was discovered through the ELISA and found to have a significant inhibitory effect on the polymerization of sickle cell hemoglobin. This work represents a novel approach for the discovery of therapeutics for this debilitating disorder.
Steenberge, Laura, "Synthesis and Screen of a Proline-Rich Combinatorial Library Towards the Identification of Sickle Cell Hemoglobin Polymerization Inhibitors" (2015). Honors Projects. 36.