Effects of macromolecular polyanions on the solubility of deoxyhemoglobin S.
The effects of four macromolecular polyanions on the equilibrium solubility of deoxy-Hb S and oxygen affinity of Hb A were evaluated. The order of molar effectiveness as gelation inhibitors was: poly-L-aspartate approximately equal to heparin (high M.W.) greater than dextran sulfate greater than heparin (low M.W.). The linear solubility profiles for the two most potent polyanions (poly-L-aspartate and high M.W. heparin) were nearly identical and reached a plateau at roughly the same sub-stoichiometric molar ratio. By contrast, poly-L-lysine, a polycation, strongly promoted gelation, while its succinylated derivative promoted gelation only marginally, as did dextran, a neutral polysaccharide. Among the seven species examined, only the four polyanions affected oxygen affinity appreciably, demonstrating the polyanions exert their solubilizing and oxygen affinity lowering effects via specific interaction with the cluster of cationic groups at the 2,3-diphosphoglycerate binding site in the central cavity of deoxyhemoglobin.
Poillon
W N
WN
Center for Sickle Cell Disease, Howard University, Washington, D.C. 20059.
Kim
B C
BC
D000838:Anions; D006451:Hemoglobin, Sickle; D006801:Humans; D046911:Macromolecular Substances; D008970:Molecular Weight; D011134:Polysaccharides / Q000494:pharmacology; D012995:Solubility
D000838:Anions; D006451:Hemoglobin, Sickle; D046911:Macromolecular Substances; D011134:Polysaccharides; C038875:deoxyhemoglobin, sickle