Modern cross-linking strategies for synthesizing acellular hemoglobin-based oxygen carriers.
Unmodified cell-free hemoglobin (Hb) is structurally unstable when transfused into the blood stream (Valeri et al., Artif Cells Blood Substit Immobil Biotechnol. 2000;28:451-475; Chan et al., Toxicol Pathol. 2000;28:635-642; Eike, Dissertation, 2005; Eike and Palmer, Biotechnol Prog. 2004;20:946-952). This review examines some of the latest chemical strategies used over the last 5 years to intra- and intermolecularly cross-link Hb, thereby stabilizing its quaternary structure. Therefore, this work will address the following aspects: (1) site-specific chemical modifications of Hb and (2) non-site-specific chemical modifications of Hb, including, but not limited to, PolyHeme, Hemopure, Oxyglobin, and SOD-Hb. Current strategies for synthesizing PEGylated Hb is outside the scope of this review and will not be discussed herein. For a more thorough review of PEGylated Hb, the reader is directed to the following works: Cabrales and Friedman, Transfus Alternatives in Transfus Med. 2007;9:281-293 and Winslow, Biochim Biophys Acta, 2008;1784(10):1382-1386.
Harris
David Raphael
DR
Dept. of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH 43210, USA.
Palmer
Andre Francis
AF
D000818:Animals; D001802:Blood Substitutes / Q000138:chemical synthesis / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000138:chemical synthesis / Q000737:chemistry*; D006454:Hemoglobins / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*
D001802:Blood Substitutes; D003432:Cross-Linking Reagents; D006454:Hemoglobins; D011108:Polymers