Improving the Stability of Maleimide-Thiol Conjugation for Drug Targeting.
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.
['Lahnsteiner|Marianne|M|http://orcid.org/0000-0002-0466-5865', 'Kastner|Alexander|A|http://orcid.org/0000-0002-4678-9997', 'Mayr|Josef|J|', 'Roller|Alexander|A|', 'Keppler|Bernhard K|BK|http://orcid.org/0000-0003-0877-1822', 'Kowol|Christian R|CR|http://orcid.org/0000-0002-8311-1632']
D003500:Cyclization D016503:Drug Delivery Systems D004355:Drug Stability D018796:Immunoconjugates D008301:Maleimides D013388:Succinimides D013438:Sulfhydryl Compounds
maleimide bioconjugation bioorganic chemistry drug delivery retro-Michael reactions