In vitro Effect of the Homocysteine Linker on Properties of Conjugates between Human Serum Albumin and Monomethyl Auristatin F
M. WANG1,2, V. I. ROGALEVA3, T. V. POPOVA1,3, O. D. ZAKHAROVA3, T. S. GODOVIKOVA3, V. N. SILNIKOV3,4
1Novosibirsk State University, Novosibirsk, Russia
2Fuzhou Fuyao Institute for Advanced Study, Fuzhou, China
3Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia
4NanoTech-S LLC, Novosibirsk, Russia
Keywords: serum albumin, homocysteine thiolactone, monomethyl auristatin F, theranostics, antitumor cytotoxicity
Abstract
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 peptide to the albumin structure and the attachment of the peptide through the N-trifluoroacetylhomocysteine linker. Confocal microscopy showed that the conjugate with the homocysteine linker effectively accumulated in the cytoplasm of the MCF-7 tumor 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.
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