Formation of cross-linked asymmetrical hybrid hemoglobins by double-headed aspirin.
Double-headed aspirin [bis(3,5-dibromosalicyl)fumarate] selectively cross-links hemoglobin molecules between Lys 82 beta 1 and Lys 82 beta 2 and increases solubility of deoxy-Hb S (Walder et al., J. Mol. Biol., 141:195, 1980 and Kikugawa et al., J. Biol. Chem., 257:7525, 1982). We reacted this reagent with the mixture of Hb A and Hb S and the mixture of Hb S and Hb York (beta 146His replaced by Pro). Cross-linked asymmetrical hybrid hemoglobins (alpha 2 beta - beta S and alpha 2 beta Y - beta S) were produced in high yields in addition to the cross-linked parent hemoglobin molecules. Results on electrophoresis, gel electrofocusing, ion exchange column chromatography, mechanical stability and oxygen binding properties showed that the cross-linked asymmetrical hybrid hemoglobins had properties intermediate between those of the cross-linked parent hemoglobins. Oxygen affinities of the cross-linked asymmetrical hybrids were not affected by the addition of 2,3-diphosphoglycerate (DPG) or inositol hexaphosphate, probably due to the presence of a fumaryl group at the DPG binding site.
D001241:Aspirin / Q000031:analogs & derivatives* / Q000494:pharmacology; D001797:Blood Protein Electrophoresis; D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004588:Electrophoresis, Cellulose Acetate; D006441:Hemoglobin A; D006451:Hemoglobin, Sickle; D006454:Hemoglobins; D006455:Hemoglobins, Abnormal; D006801:Humans; D010108:Oxyhemoglobins / Q000032:analysis
D003432:Cross-Linking Reagents; D006451:Hemoglobin, Sickle; D006454:Hemoglobins; D006455:Hemoglobins, Abnormal; D010108:Oxyhemoglobins; C021630:bis(3,5-dibromosalicyl)fumarate; C038621:hemoglobin York; D006441:Hemoglobin A; D001241:Aspirin