Abstract
Abstract As a hemoglobin (Hb)-based oxygen carrier (HBOC), Hb suffers from the disadvantages of short half-life, renal toxicity and vasoactivity. Because dextran is a macromolecule that can be easily derivatized with various chemical moieties, conjugation of Hb with dextran can effectively increase the size of Hb and overcome the disadvantages of Hb. Thus, a dextran-bovine Hb (bHb) conjugate (dex-bHb) was prepared by conjugation of bHb with periodate-oxidized dextran here. As an important functional amino acid residue of bHb, Cys-93(β) was reversibly protected by 4,4′-dithiodipyridine to avoid reaction with periodate-oxidized dextran. Dex-bHb showed significantly higher hydrodynamic volume and higher viscosity than bHb. Conjugation with dextran stabilized the R state of bHb and slightly altered the heme environment of bHb. Conjugation with dextran decreased the P50 of bHb, lowered the sensitivity to the allosteric effectors and slightly decreased the autoxidation rate of bHb. Thus, dex-bHb was expected to act as a potent HBOC with low oxidative toxicity.
Published Version
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