Harris David Raphael, Palmer Andre Francis
Dept. of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH 43210, USA.
Biotechnol Prog. 2008 Nov-Dec;24(6):1215-25. doi: 10.1002/btpr.85.
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.
未修饰的无细胞血红蛋白(Hb)输注到血流中时结构不稳定(瓦莱里等人,《人工细胞、血液替代品与固定化生物技术》。2000年;28:451 - 475;陈等人,《毒理病理学》。2000年;28:635 - 642;艾克,博士论文,2005年;艾克和帕尔默,《生物技术进展》。2004年;20:946 - 952)。本综述考察了过去5年中用于血红蛋白分子内和分子间交联的一些最新化学策略,从而稳定其四级结构。因此,本研究将涉及以下几个方面:(1)血红蛋白的位点特异性化学修饰和(2)血红蛋白的非位点特异性化学修饰,包括但不限于多聚血红素、血纯、氧合球蛋白和超氧化物歧化酶 - 血红蛋白。目前合成聚乙二醇化血红蛋白的策略不在本综述范围内,在此不予讨论。关于聚乙二醇化血红蛋白更全面的综述,读者可参考以下著作:卡布拉斯和弗里德曼,《输血医学中的输血替代方法》。2007年;9:281 - 293以及温斯洛,《生物化学与生物物理学报》,2008年;1784(10):1382 - 1386。