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Improving the Stability of Maleimide–Thiol Conjugation for Drug Targeting
Author(s) -
Lahnsteiner Marianne,
Kastner Alexander,
Mayr Josef,
Roller Alexander,
Keppler Bernhard K.,
Kowol Christian R.
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202003951
Subject(s) - maleimide , thiol , chemistry , conjugate , combinatorial chemistry , glutathione , adduct , drug , organic chemistry , pharmacology , enzyme , mathematical analysis , mathematics , medicine
Maleimides are essential compounds for drug conjugation reactions via thiols to antibodies, peptides and other targeting units. However, one main drawback is the occurrence of thiol exchange reactions with, for example, glutathione resulting in loss of the targeting ability. A new strategy to overcome such retro‐Michael exchange processes of maleimide–thiol conjugates by stabilization of the thiosuccinimide via a transcyclization reaction is presented. This reaction enables the straightforward synthesis of stable maleimide–thiol adducts essential in drug‐conjugation applications.