Human Serum Albumin Domain I Fusion Protein for Antibody Conjugation.
Human Serum Albumin Domain I Fusion Protein for Antibody Conjugation.
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DOI：
10.1021/acs.bioconjchem.6b00432
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发表时间：
2016-10-19
影响因子：
4.7
通讯作者：
Barbas CF 3rd
中科院分区：
文献类型：
--
作者：
Patterson JT;Wilson HD;Asano S;Nilchan N;Fuller RP;Roush WR;Rader C;Barbas CF 3rd
抗体的生物正交标记使得能够缀合化合物，例如小分子或肽，其扩大靶向能力或增强细胞毒性。利用的环己烯磺酰胺化合物，位点选择性地标记Lys 64在人血清白蛋白（HSA），我们证明，结构域I的HSA可以用作融合蛋白的抗体偶联物的制备。曲妥珠单抗融合体在轻链的N-末端或重链的C-末端表达，从而能够与小分子缀合。此外，这些缀合物保留了HER 2结合，并证明在人血浆中高度稳定。因此，通过HSA结构域I融合的抗体缀合对于制备血清稳定的抗体缀合物，特别是抗体-药物缀合物具有广泛的用途。
Bioorthogonal labeling of antibodies enables the conjugation of compounds, such as small molecules or peptides, which expand targeting capacity or enhance cytotoxicity. Taking advantage of a cyclohexene sulfonamide compound that site-selectively labels Lys64 in human serum albumin (HSA), we demonstrate that domain I of HSA can be used as a fusion protein for the preparation of antibody conjugates. Trastuzumab fusions were expressed at the N-terminus of the light chain or the C-terminus of the heavy chain enabling conjugation to small molecules. Moreover, these conjugates retained HER2 binding and proved to be highly stable in human plasma. Antibody conjugation via HSA domain I fusion should therefore have broad utility for making serum-stable antibody conjugates, particularly for antibody-drug conjugates.