IN VITRO EFFECT OF THE HOMOCYSTEINE LINKER ON PROPERTIES OF CONJUGATES BETWEEN HUMAN SERUM ALBUMIN AND MONOMETHYL AURISTATIN F

Fluorescent conjugates of human serum albumin and a maleimide derivative of monomethyl auristatin F containing the cleavable peptide linker ValCit were synthesised. Strategies included the direct attachment of the therapeutic peptide to the albumin structure and attachment through the N-trifluoroacetylhomocysteine linker. Confocal microscopy showed that the conjugate with the homocysteine linker effectively accumulated in the cytoplasm of the MCF-7 tumour cells, whereas the conjugate without the linker displayed predominant surface accumulation. In vitro studies demonstrated that the monomethyl auristatin F conjugate exhibited enhanced cytotoxicity against MCF-7 and T98G cancer cells after its attachment to albumin. The homocysteine-containing conjugate showed superior cytotoxicity compared to the conjugate without the linker despite the lower peptide load.