Bissulfosuccinimidyl esters of aliphatic dicarboxylic acids: a new class of 'affinity directed' beta beta crosslinkers of HbA.

The potential of sulfosuccinimidyl ester of suberic acid as an intramolecular crosslinker of HbA, directed to the positive charge rich domain of the protein (DPG pocket) has been investigated. The suberate ester introduced crosslinks between the beta-chains and inhibited the dissociation of HbA into alpha beta dimers. The facile crosslinking reaction seen with this suberate ester as compared to the absence of crosslinking with the diaspirin derivative of suberic acid suggests the strong 'steering' influence of the sulfosuccinimidyl moiety of the reagent to the targeted site. The application of this crosslinking approach in the preparation of Hb based blood substitutes is discussed.