Effect of NaBH4 concentration and reaction time on physical properties of glutaraldehyde-polymerized hemoglobin

Effect of NaBH4 concentration and reaction time on physical properties of glutaraldehyde-polymerized hemoglobin
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DOI:
10.1021/bp0343155
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发表时间:
2004-05-01
影响因子:
2.9
通讯作者:
Palmer, AF
Palmer, AF
中科院分区:
工程技术4区
文献类型:
--
作者:
Eike, JH;Palmer, AF

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美国大约还有1.5天就会耗尽其全部血液供应。因此,迫切需要开发通用的血液替代品。一种这样的血液替代品是戊二醛聚合的牛血红蛋白。尽管戊二醛聚合的牛血红蛋白为基础的血液替代品的商业开发,很少有发表的工作的影响,反应条件的聚合血红蛋白分散体的物理性质。在这项研究中,通过测量绝对分子量分布,以及氧结合性能,如P-50,希尔系数,和高铁血红蛋白水平(MetHb)的这些分散体的不同浓度的猝灭剂NaBH 4,戊二醛浓度,和反应时间对PolyHb分散体的物理性质的影响进行了研究。牛血红蛋白与戊二醛使用平行合成方法聚合。采用不对称流场-流分级分离技术(AFFF)结合多角度静态光散射(MASLS)测定了PolyHb分散体的绝对分子量分布。一般而言,高戊二醛浓度(血红蛋白摩尔浓度的20-30倍)对PolyHb分散体的氧结合性质产生不利影响,而NaBH 4浓度(高达血红蛋白摩尔浓度的300倍)和反应时间(高达24小时)似乎对PolyHb分散体的氧结合性质没有任何影响。
The US is about 1.5 days away from exhausting its entire blood supply. Hence, there is an urgent need for the development of universal blood substitutes. One such blood substitute is glutaraldehyde-polymerized bovine hemoglobin. Despite the commercial development of glutaraldehyde-polymerized bovine hemoglobin-based blood substitutes, there has been little published work on the effect of reaction conditions on the physical properties of the polymerized hemoglobin dispersion. In this study, the effect of varying the concentration of the quenching agent NaBH4, glutaraldehyde concentration, and reaction time on the physical properties of PolyHb dispersions was studied by measuring the absolute molecular weight distribution, as well as oxygen-binding properties such as P-50, Hill coefficient, and methemoglobin level (MetHb) of these dispersions. Bovine hemoglobin was polymerized with glutaraldehyde using a parallel synthetic approach. Asymmetric flow field-flow fractionation (AFFF) coupled with multi-angle static light scattering (MASLS) was used to measure the absolute molecular weight distribution of the PolyHb dispersions. In general, high glutaraldehyde concentrations (20-30 times the molar concentration of hemoglobin) adversely affected the oxygen-binding properties of PolyHb dispersions, while NaBH4 concentrations (up to 300 times the molar concentration of hemoglobin) and reaction times (up to 24 h) did not appear to have any effect on the oxygen-binding properties of PolyHb dispersions.