MAPN: First-in-Class Reagent for Kinetically Resolved Thiol-to-Thiol Conjugation

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• 作者：Oleksandr Koniev ; Sergii Kolodych ; Zoljargal Baatarkhuu ; Johann Stojko ; Jitka Eberova ; Jean-Yves Bonnefoy ; Sarah Cianf茅rani ; Alain Van Dorsselaer ; Alain Wagner
• 刊名：Bioconjugate Chemistry
• 出版年：2015
• 出版时间：September 16, 2015
• 年：2015
• 卷：26
• 期：9
• 页码：1863-1867
• 全文大小：347K
• ISSN：1520-4812

文摘

Thiols are among the most frequently used functional groups in the field of bioconjugation. While there exists a variety of heterobifunctional reagents that allow for coupling thiols to other functions (e.g., amines, carboxylic acids), there is no specific reagent for creating heteroconjugates using two different thiols. In response to the ever-increasing demand for bioconjugation tools, we have developed p-(maleimide)-phenylpropionitrile (MAPN)鈥攁n efficient reagent for kinetically resolved thiol-to-thiol coupling. In a comparative study with its closest commercially available analogue, p-phenylenedimaleimide, MAPN has shown substantial advantages for the preparation of thiol鈥搕hiol heteroconjugates. Namely, an antibody鈥揹rug conjugate (ADC) with mertansine (DM1), conjugated to the cysteine residues of Trastuzumab, was prepared for the first time.