Publisher Summary This chapter focuses on hemoglobin polymerization. A reagent to cross-link hemoglobin (Hb) is needed to stabilize the tetramer (64 kDa) by intramolecular cross-links and to produce oligomers ( 500 kDa) by intermolecular cross-links. Intramolecular cross-links between tetramer subunits prevent dissociation into excretable dimers (32 kDa). Intermolecular cross-links are necessary to reduce colloid osmotic pressure as well as to improve the circulatory half-life of the molecule as a cell-free solution. The chapter introduces a reliable two-step procedure in which the crosslinking is performed by a simple molecule and the oxygen affinity is modified by a separate simple molecule. Glycolaldehyde is a very useful, flexible, reliable, and cost-effective option in the spectrum of chemical reagents available for the modification of Hb solutions. It is remarkably compatible with a variety of additional chemical derivatives (2-nor-2-formylpyridoxal 5'-phosphate (NFPLP) and bis(3,5-dibromosalicyl) fumarate (DBBF)) and the oxy and deoxy forms of Hb. The use of glycolaldehyde in the scaleup of Hb modification and processing on a large scale for the production of therapeutic, clinical grade material maybe realistically contemplated.
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