Sabar Muhammad Farooq, Kausar Samra, Zafar Ahmad Usman
Centre for Applied Molecular Biology, Ministry of Science and Technology, Lahore, Pakistan.
Pak J Pharm Sci. 2013 Mar;26(2):425-30.
Di-branched (Y-shaped) polyethylene glycols (PEGs) are considered more effective than linear molecules to enhance the efficacy of the conjugated drug. In the present study interferon α-2a was conjugated with three different 40 KDa di-branched PEGs. The results of this study show that length and/or the structure of linker between PEG and the protein is also involved in the synthesis, in vitro biological activity and stability of the conjugate. Three conjugates i.e., mPEG2L-IFN, mPEG2P-IFN and mPEG(2)M-IFN yielded 25%, 24% and 17%, with bioactivities 2.8 x 10(6) IU/mg, 3.95 x 10(6) IU/mg and 6.7 x 10(6) IU/mg, respectively. The order of bioactivity stability is mPEG2L-IFN > mPEG2P-IFN > mPEG2M-IFN > IFN (native). We report that although lengthy linkers are more reactive in terms of conjugation, they have opposite effect on the in vitro bioactivity of the conjugate. PEGylation as a whole increases the stability of the conjugate, and linkers also add in stability.
双分支（Y形）聚乙二醇（PEG）被认为比线性分子在增强偶联药物疗效方面更有效。在本研究中，将干扰素α-2a与三种不同的40 kDa双分支PEG进行偶联。本研究结果表明，PEG与蛋白质之间连接子的长度和/或结构也参与了偶联物的合成、体外生物活性和稳定性。三种偶联物，即mPEG2L-IFN、mPEG2P-IFN和mPEG(2)M-IFN的产率分别为25%、24%和17%，生物活性分别为2.8×10(6) IU/mg、3.95×10(6) IU/mg和6.7×10(6) IU/mg。生物活性稳定性顺序为mPEG2L-IFN > mPEG2P-IFN > mPEG2M-IFN > 天然干扰素（IFN）。我们报道，尽管长连接子在偶联方面反应性更高，但它们对偶联物的体外生物活性有相反的影响。整体而言，聚乙二醇化增加了偶联物的稳定性，连接子也有助于提高稳定性。
