Effect of cross-linker length on the stability of hemoglobin.
A series of cross-linking reagents with 4 to 7 carbons have been synthesized and used to modify human hemoglobin. The product yields and biochemical properties of these cross-linked hemoglobins are compared to those made with both longer and shorter cross-linkers. Several trends become apparent. The yields decrease as the cross-linker becomes longer, which correlates well with molecular dynamics studies of reagent binding pathways presented here. The autooxidation rates increase while thermal stability decreases with longer reagents. Cross-linking under deoxy conditions also increases autooxidation rates, but the effect is less than that of increased cross-linker length. The results suggest that shorter reagents may provide better-stabilized tetramers for the construction of more complex hemoglobin-based oxygen carriers.
Bobofchak
Kevin M
KM
Loyola University Chicago, Department of Chemistry, Chicago, Illinois 60626, USA.
Tarasov
Eugene
E
Olsen
Kenneth W
KW
D001774:Blood Chemical Analysis; D002210:Caprylates; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000494:pharmacology*; D003998:Dicarboxylic Acids; D004355:Drug Stability; D005977:Glutarates; D006454:Hemoglobins / Q000737:chemistry* / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D010084:Oxidation-Reduction; D010108:Oxyhemoglobins / Q000737:chemistry* / Q000302:isolation & purification; D011485:Protein Binding; D011489:Protein Denaturation; D012459:Salicylates / Q000097:blood / Q000737:chemistry; D013386:Succinates; D013816:Thermodynamics
D002210:Caprylates; D003432:Cross-Linking Reagents; D003998:Dicarboxylic Acids; D005977:Glutarates; D006454:Hemoglobins; D010108:Oxyhemoglobins; D012459:Salicylates; D013386:Succinates; C005738:suberic acid