Effect of cross-linker length on the stability of hemoglobin

Effect of cross-linker length on the stability of hemoglobin
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DOI:
10.1016/j.bbapap.2008.01.014
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发表时间:
2008-10-01
影响因子:
3.2
通讯作者:
Olsen, Kenneth W.
Olsen, Kenneth W.
中科院分区:
生物学3区
文献类型:
--
作者:
Bobofchak, Kevin M.;Tarasov, Eugene;Olsen, Kenneth W.

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合成了一系列碳原子数为4 ~ 7的交联剂,并用于修饰人血红蛋白。将这些交联血红蛋白的产物产率和生物化学性质与用较长和较短交联剂制备的血红蛋白进行比较。几个趋势变得明显。随着交联剂变长,产率降低,这与本文所提出的试剂结合途径的分子动力学研究很好地相关。随着反应时间的延长,自氧化速率增加,而热稳定性降低。在脱氧条件下交联也增加自氧化速率,但效果小于增加交联剂长度。结果表明,较短的试剂可以提供更好的稳定的四聚体的建设更复杂的血红蛋白为基础的氧载体。(C)2008 Elsevier B. V.保留所有权利。
A series of cross-linking reagents with 4 to 7 carbons have been synthesized and used to modify human hemoglobin. The product yields and biochemical properties of these cross-linked hemoglobins are compared to those made with both longer and shorter cross-linkers. Several trends become apparent. The yields decrease as the cross-linker becomes longer, which correlates well with molecular dynamics studies of reagent binding pathways presented here. The autooxidation rates increase while thermal stability decreases with longer reagents. Cross-linking under deoxy conditions also increases autooxidation rates, but the effect is less than that of increased cross-linker length. The results suggest that shorter reagents may provide better-stabilized tetramers for the construction of more complex hemoglobin-based oxygen carriers. (C) 2008 Elsevier B.V. All rights reserved.