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

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...

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Bibliographic Details
Published in:Bioconjugate chemistry 2015-09, Vol.26 (9), p.1863-1867
Main Authors: Koniev, Oleksandr, Kolodych, Sergii, Baatarkhuu, Zoljargal, Stojko, Johann, Eberova, Jitka, Bonnefoy, Jean-Yves, Cianférani, Sarah, Van Dorsselaer, Alain, Wagner, Alain
Format: Article
Language:English
Subjects:
Alkynes - chemistry
Biochemistry
Biochemistry, Molecular Biology
Cell Line, Tumor
Chemistry
Comparative analysis
Humans
Immunoconjugates - chemistry
Indicators and Reagents - chemistry
Kinetics
Life Sciences
Maleimides - chemistry
Sulfhydryl Compounds - chemistry
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Summary: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)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.
ISSN:1043-1802
1520-4812
DOI:10.1021/acs.bioconjchem.5b00440