Improving the Stability of Maleimide-Thiol Conjugation for Drug Targeting

Author(s)
Marianne Lahnsteiner, Alexander Kastner, Josef Mayr, Alexander Roller, Bernhard K. Keppler, Christian R. Kowol
Abstract

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.

Organisation(s)
Department of Inorganic Chemistry, Core Facility Crystal Structure Analysis
External organisation(s)
Research Cluster Translational Cancer Therapy Research
Journal
Chemistry: A European Journal
Volume
26
Pages
15867-15870
No. of pages
4
ISSN
0947-6539
DOI
https://doi.org/10.1002/chem.202003951
Publication date
12-2020
Peer reviewed
Yes
Austrian Fields of Science 2012
301207 Pharmaceutical chemistry, 301206 Pharmacology
Keywords
ASJC Scopus subject areas
Catalysis, Organic Chemistry
Portal url
https://ucrisportal.univie.ac.at/en/publications/cd62e564-ee37-4128-9e49-5066ea9f9bc8