Hu Tao, Li Dongxia, Meng Fantao, Prabhakaran Muthuchidambaram, Acharya Seetharama A
Department of Physiology and Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Artif Cells Blood Substit Immobil Biotechnol. 2011 Apr;39(2):69-78. doi: 10.3109/10731199.2010.501756. Epub 2010 Jul 23.
The propensity of site-specific carboxymethylation and propylation of Val-1(α) of Hb to attenuate the reductive hexaPEGylation-induced dissociation of tetramers has been investigated. Only reductive propylation of Val-1(α), which increases the stability of oxy Hb, attenuates the reductive hexaPEGylation-induced dissociation. Increasing the stability of the oxy conformation of Hb by chemical or genetic approaches is a strategy to generate PEGylated Hbs with native-like tetramer stability using direct PEGylation platforms. This new approach and EAF-PEGylation are the only two alternate PEGylation strategies available to design stable second-generation vasoinactive uncrosslinked PEGylated Hbs with native-like tetramer stability.
已对血红蛋白α链1位缬氨酸位点特异性羧甲基化和丙基化减弱六聚乙二醇还原诱导的四聚体解离的倾向进行了研究。只有α链1位缬氨酸的还原丙基化增加了氧合血红蛋白的稳定性，减弱了六聚乙二醇还原诱导的解离。通过化学或基因方法提高血红蛋白氧构象的稳定性是一种使用直接聚乙二醇化平台生成具有天然四聚体稳定性的聚乙二醇化血红蛋白的策略。这种新方法和EAF聚乙二醇化是仅有的两种可用于设计具有天然四聚体稳定性的稳定第二代血管惰性非交联聚乙二醇化血红蛋白的替代聚乙二醇化策略。
