p-nitrobentsyylin pelkistyksen ja S9 maksasolufraktioiden käyttö ennustamaan vastaaine konjugoitujen lääkkeiden irtoamista biologisessa ympäristössä

Antibody-drug conjugates (ADCs) are an advancing class of pharmaceuticals, particularly in the field of oncology. A core element of drug conjugate technology is the linker component, which determines the release properties for the conjugated pharmaceutical payloads. As each component of a full ADC can be complex, it is desirable to design methods to screen individual components separately. In this thesis the reduction of para-nitrobenzyl is tested to predict the kinetics of payload selfimmolation. It was found that the system is an adequate method for qualitative screening of different payloads of similar class, such as phenols. As a novel concept, sulfonamides were tested for their feasibility as a linking moiety for attachment to linker molecules. In addition, a human liver S9 assay designed for full ADCs was investigated for the feasibility of studying linker-payload constructs by themselves. It was found that the assay provides qualitative data for ranking the cleavage speeds of different linkers. Finally, through an extensive literature portion, the thesis aims to deliver a thorough overall view into drug-conjugate technology to serve as an introduction into the subject.