Structural and Redox Behavior of OxyVita™, a Zero-linked Polymeric Hemoglobin: Comparison with Natural Acellular Polymeric Hemoglobins
Structural and Redox Behavior of OxyVita™, a Zero-linked Polymeric Hemoglobin: Comparison with Natural Acellular Polymeric Hemoglobins
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DOI：
10.3109/10731191003634562
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发表时间：
2010-04-01
期刊：
影响因子：
--
通讯作者：
Wollocko, Hanna
中科院分区：
文献类型：
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作者：
Harrington, John P.;Orlig, Kseniya;Wollocko, Hanna
一种零连接聚合物血红蛋白(OxyVita HB)已被开发为一种脱细胞治疗性血红蛋白氧载体(HBOC)。为了有效和安全地结合、运输和输送氧，HBOC必须满足与其结构完整性和氧化还原稳定性相关的基本分子要求。OxyVita(TM)是一种具有平均相对分子质量的超级聚合物。17×10(6)Da。结构完整性是通过在尿素浓度增加的情况下对OxyVita(TM)进行展开研究来确定的。将OxyVita(TM)不同制剂(溶液和粉末形式)的展开中点(D-1/2)与天然无细胞聚合血红蛋白Lumbricus Hb(Ltd.Hb)和Arenicola Hb(ArHb)进行比较，这两种天然无细胞聚合血红蛋白可作为有效和安全的无细胞HBOC的模型。还研究了使用内源还原剂对OxyVita Hb进行还原的研究。这些研究结果表明：1)OxyVita Hb在还原(OxHb)状态下对构象变化的抵抗力比LtHb或ArHb更大；2)在抗坏血酸或抗坏血酸的存在下，Met OxyVita Hb还原为OxHb的速度很慢(560min内还原70%)。或β-NADH(90分钟内减少40%)。这些研究提供了一致的证据，证明OxyVita HB具有显示出结构完整性和氧化还原行为的物理化学性质，这是在临床应用中作为有效和安全的HBOC所必需的。这些结果与其他研究人员关于OxyVita HB减少血红素丢失的观察结果一致，OxyVita HB对于循环系统内分子氧的可逆结合/释放是必不可少的。
A zero-linked polymeric hemoglobin (OxyVita Hb) has been developed for application as an acellular therapeutic hemoglobin-based-oxygen-carrier (HBOC). For effective and safe oxygen binding, transport and delivery, an HBOC must meet essential molecular requirements related to its structural integrity and redox stability. OxyVita (TM) is a super polymer possessing an average M.wt. of 17 x 10(6) Da. Structural integrity was determined by unfolding studies of OxyVita (TM) in the presence of increasing concentrations of urea. The unfolding midpoints (D-1/2) of different preparations of OxyVita (TM) (solution and powder forms) were compared to Lumbricus Hb (LtHb) and Arenicola Hb (ArHb), natural acellular polymeric hemoglobins, which are serving as models for an effective and safe acellular HBOC. Reduction studies of OxyVita Hb using endogenous reducing agents were also investigated. Results from these studies indicate that: 1) OxyVita Hb exhibits greater resistance to conformational change than either LtHb or ArHb in the reduced (oxyHb) state; and 2) the reduction of met OxyVita Hb to oxyHb occurs slowly in the presence of either ascorbic acid (70% reduction in 560 min.) or beta-NADH (40% reduction in 90 min.). These studies provide consistent evidence that OxyVita Hb possesses physiochemical properties that exhibit structural integrity and redox behavior necessary for functioning as an effective and safe HBOC within clinical applications. These results are in agreement with observations made by other investigators as to the reduction in heme-loss of OxyVita Hb, essential for the reversible binding/release of molecular oxygen within the circulatory system.