Halogenation at the Phenylalanine Residue of Monomethyl Auristatin F Leads to a Favorable cis/trans Equilibrium and Retained Cytotoxicity.

ABSTRACT: Halogenation can be utilized for the purposes of labeling and molecular imaging, providing a means to, e.g., follow drug distribution in an organism through positron emission tomography (PET) or study the molecular recognition events unfolding by nuclear magnetic resonance (NMR) spectroscopy. For cancer therapeutics, where often highly toxic substances are employed, it is of importance to be able to track the distribution of the drugs and their metabolites in order to ensure minimal side effects. Labeling should ideally have a negligible disruptive effect on the efficacy of a given drug. Using a combination of NMR spectroscopy and cytotoxicity assays, we identify a site susceptible to halogenation in monomethyl auristatin F (MMAF), a widely used cytotoxic agent in the antibody-drug conjuga

SUBMITTER: Sokka IK 

PROVIDER: S-EPMC8397390 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature