聚乙二醇大分子化猪血红蛋白对其携氧特性的影响

The Influence on Oxgen carrying Capacity of Porcine Hemoglobin while Attached PEG to Increase its Total Molecular Weight

用PEG共轭结合猪血红蛋白(pHb)以增大总分子量是延长它在血液循环系统中存留时间的有效方法。作为一种线性的亲水大分子,PEG对pHb的共轭会对它的携氧特性产生显著影响。研究了pHb处于不同空间构象(脱氧的T构象或氧合的R构象)、PEG修饰程度的高低、修饰用PEG的分子量的大小、有无别构效应调节剂等不同条件下PEG修饰对pHb携氧能力的影响。进而又用了PEG修饰已经用双(3,5二溴水杨酸)延胡索酸酯(DBBF)分子内交联的pHb,考察修饰对这种内交联pHb携氧功能的影响。还比较了4种不同方法活化的PEG衍生物,对pHb修饰效率、对修饰产物携氧功能的影响及修饰产物稳定性等。本文认为,DBBF分子内交联的pHb,在有别构效应调节剂的存在下,再用PEG修饰,可以获得携氧能力好、分子量适宜、四聚体稳定的修饰产物。

Increasing the total molecular weight of hemoglobin through PEG modification has been proved to be a better choice in prolonging vascular retention time.As a long,linear,hydrophilic molecular,PEG exerts significant influence on the oxygen carrying properties of porcine hemoglobin (pHb) when attached.PEG hemoglobins exhibit a wide range of differences in their properties depending on which molecular weight PEG is selected,how many PEGs are bound and whether the allosteric cofactors exist or not.Furthermore,DBBF intracross linked pHbs are bound to various active PEG.As a result,with the combination of the three methods:DBBF intracross linking,allosteric cofactors involving and PEG conjugating,a tetramer stable and high oxygen carrying capacity pHb derivitive with large molecular weight is obtained.