Polymerization of human hemoglobin using the crosslinker 1,11-bis(maleimido)triethylene glycol for use as an oxygen carrier.
Polymerization of human hemoglobin using the crosslinker 1,11-bis(maleimido)triethylene glycol for use as an oxygen carrier.
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使用交联剂 1,11-双（马来酰亚胺基）三甘醇作为氧载体聚合人血红蛋白。
DOI：
10.1002/btpr.467
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发表时间：
2010
影响因子：
2.9
通讯作者：
Palmer,AndreF
中科院分区：
文献类型：
--
作者：
Zhang,Ning;Palmer,AndreF
血管收缩和全身性高血压是目前商业聚合血红蛋白(PolyHbs)输注的主要副作用。据推测，在PolyHb溶液中存在的游离四聚体血红蛋白(Hb)是这些副作用的根本原因。因此，增加PolyHbs的大小和减少溶液中游离Hb的数量应该会双重减少血管收缩和全身性高血压的程度。然而，目前所有商品化的PolyHb制剂在溶液中都有一小部分游离Hb。因此，迫切需要开发新的化学策略来合成聚合度较高的大分子聚Hb，而不需要溶液中的游离Hb。在本研究中，以双马来酰亚胺聚乙二醇衍生物(1，11-双(马来酰亚胺)三甘醇)聚合人血红蛋白，合成了一种基于Hb的氧载体。所得聚Hb的重均相对分子质量为1.49±0.62MDA，氧亲和力(P50)为2.75±0.55 mm Hg，Hill系数(N)为0.97±0.07。光散射分析证实，溶液中不存在游离的Hb单体、二聚体和四聚体。这项工作意义重大，因为它应该使非血管活性聚Hbs的未来工程具有潜在的应用于输血医学。©2010美国化学工程师学会生物技术。节目，2010年
Vasoconstriction and systemic hypertension are the main side effects associated with transfusion of current commercial polymerized hemoglobins (PolyHbs). It is hypothesized that the presence of free tetrameric hemoglobin (Hb) in the PolyHb solution is the root cause of these side effects. Therefore, increasing the size of PolyHbs and reducing the amount of free Hb in solution should dually reduce the extent of vasoconstriction and systemic hypertension. However, all current commercial PolyHb preparations have a small fraction of free Hb in solution. Hence, there is an urgent need to develop novel chemical strategies to synthesize large PolyHb molecules with a higher degree of polymerization without free Hb in solution. In this study, a Hb‐based oxygen carrier was synthesized by polymerizing human Hb using a dimaleimide poly(ethylene glycol) derivative (1,11‐bis(maleimido)triethylene glycol). The resultant PolyHb has a weight‐averaged molecular weight of 1.49 ± 0.62 MDa, O2affinity (P50) of 2.75 ± 0.55 mm Hg, and Hill coefficient (n) of 0.97 ± 0.07. Light scattering analysis of the PolyHb dispersion confirmed the absence of free Hb monomers, dimers, and tetramers in solution. This work is significant, as it should enable future engineering of nonvasoactive PolyHbs with potential applications in transfusion medicine. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010