Abstract
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.