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

作者：Koniev Oleksandr; Kolodych Sergii; Baatarkhuu Zoljargal; Stojko Johann; Eberova Jitka; Bonnefoy Jean Yves; Cianferani Sarah; Van Dorsselaer Alain; Wagner Alain^*

来源：Bioconjugate Chemistry, 2015, 26(9): 1863-1867.

DOI：10.1021/acs.bioconjchem.5b00440

Thiols are among the most frequently used functional groups in the field of bio conjugation. 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)-an 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 thiol heteroconjugates. Namely, an antibody drug conjugate (ADC) with mertansine (DM1), conjugated to the cysteine residues of Trastuzumab, was prepared for the first time.

• 出版日期2015-9