Antisickling activity of amino acid benzyl esters.
The sickling of homozygous sickel cells upon deoxygenation is inhibited in the presence of 3 mM L-phenylalanine benzyl ester (Phe-OBzl) or benzyl esters of other aromatic or hydrophobic amino acids. Phe-OBzl was found to permeate into erythrocytes rapidly, and the deoxygenated cells maintained considerable flexibility as measured by their ability to pass through 3-micron pores. The osmotic fragility of the cells was unchanged and the oxygen dissociation curve was shifted slightly from a 50% saturation values of 28.5 mm Hg to 31.0 mm Hg. At lower concentrations of Phe-OBzl some antisickling activity was seen. The Phe-OBzl antisickling activity may involve both binding to deoxyhemoglobin S and modification of the erythrocyte membrane. This class of compounds has considerable potential as therapeutic agents for the treatment of sickle cell disease.
D000596:Amino Acids / Q000494:pharmacology*; D000755:Anemia, Sickle Cell / Q000097:blood; D000986:Antisickling Agents; D001593:Benzyl Compounds / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D009996:Osmotic Fragility; D010100:Oxygen / Q000097:blood; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000596:Amino Acids; D000986:Antisickling Agents; D001593:Benzyl Compounds; D010649:Phenylalanine; C023629:phenylalanine O-benzyl ester; D010100:Oxygen