Faculty of Chemistry, Institute of Inorganic Chemistry, University of Vienna, Waehringer Strasse 42, 1090, Vienna, Austria.
Research Cluster "Translational Cancer Therapy Research", Waehringer Strasse 42, 1090, Vienna, Austria.
Chemistry. 2020 Dec 4;26(68):15867-15870. doi: 10.1002/chem.202003951. Epub 2020 Oct 27.
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.
马来酰亚胺是通过巯基将药物与抗体、肽和其他靶向单元连接的重要化合物。然而，一个主要的缺点是与例如谷胱甘肽发生巯基交换反应，导致靶向能力丧失。本文提出了一种通过反环化反应稳定硫代琥珀酰亚胺来克服马来酰亚胺-巯基缀合物的这种逆向迈克尔交换过程的新策略。该反应能够直接合成药物偶联应用中必不可少的稳定马来酰亚胺-巯基加合物。
