Amino Acid and Peptide Approaches to Anti-sickling Agents

Abstract

Sickle cell anemia is a genetic disease that affects a large number of people throughout the world. This disease is very well understood at the molecular level, but for which there is still no effective treatment or cure. Phenylalanine, a natural amino acid, has long been known to inhibit the aggregation of sickle hemoglobin (HbS) that leads to the symptoms of sickle cell anemia. However, phenylalanine is weakly potent and thus limited as a potential treatment. Various investigators have developed approaches that seek to improve the effectiveness of amino acid and peptide analogues as anti-sickling agents. These are discussed here in some detail, in addition to a summary of some recent approaches utilizing computer assisted drug design (CADD). CADDis used to understand the potential binding pockets on hemoglobin and to design effective ligands that are more potent as anti-sickling agents. Recently synthesized peptides are considerably more potent than phenylalanine and offer hope that an effective treatment can be developed soon.