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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。
Conjugation of porcine hemoglobin (pHb) with PEG to increase the total molecular weight is an effective method of extending its retention in the blood circulatory system. As a linear hydrophilic macromolecule, conjugation of PEG to pHb can have a significant effect on its oxygen carrying properties. The effects of PEG modification on the pHb, such as the conformational or oxygen conformation of R, in different spatial conformations (deoxygenation T conformation or oxygenation conformation), the degree of PEG modification, the molecular weight of PEG, the presence or absence of allosteric modulators, Effect of oxygen capacity. In turn, PEG was used to modify the pHb that had been crosslinked intramolecularly with bis (3,5 dibromosalicylic acid) fumarate (DBBF) to investigate the effect of modification on the oxygen carrying capacity of this internal cross-linked pHb. Four kinds of PEG derivatives activated by different methods were also compared, the efficiency of pHb modification, the oxygen carrying function of modified products and the stability of modified products were also compared. In this paper, DBbF molecular cross-linked pHb, in the presence of allosteric effect modifier, and then modified with PEG, can be carried oxygen carrying capacity, molecular weight suitable tetramer stability modified products.