Abstract: As the most abundant protein with a variety of physiological functions, albumin has been used extensively for the delivery of therapeutic molecules. Thiolactone chemistry provides a powerful tool to prepare spin-labeled albumin-based multimodal imaging probes and therapeutic agents. We report the synthesis of a tamoxifen homocysteine thiolactone derivative and its use in thiol-'click' chemistry to prepare multi-functionalized serum albumin. The released sulfhydryl group of the homocysteine functional handle was labeled with a nitroxide reagent to prepare a spin-labeled albumin-tamoxifen conjugate confirmed by MALDI-TOF-MS, EPR spectroscopy, UV-vis and fluorescent emission spectra. This is the basis for a novel multimodal tamoxifen-albumin theranostic with a significant (dose-dependent) inhibitory effect on the proliferation of malignant cells. The response of human glioblastoma multiforme T98G cells and breast cancer MCF-7 cells to tamoxifen and its albumin conjugates was different in tumor cells with different expression level of ER alpha in our experiments. These results provide further impetus to develop a serum protein for delivery of tamoxifen to cancer cells.

Cite: Popova T. , Krumkacheva O.A. , Burmakova A.S. , Spitsyna A.S. , Zakharova O.D. , Lisitskiy V.A. , Kirilyuk I.A. , Silnikov V.N. , Bowman M.K. , Bagryanskaya E.G. , Godovikova T.S.
Protein modification by thiolactone homocysteine chemistry: a multifunctionalized human serum albumin theranostic
RSC Medicinal Chemistry. 2020. V.11. N11. P.1314-1325. DOI: 10.1039/c9md00516a WOS Scopus РИНЦ OpenAlex

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Identifiers:

Web of science:	WOS:000591526600005
Scopus:	2-s2.0-85096512911
Elibrary:	45134412
OpenAlex:	W3014959539

Citing:

DB	Citing
Web of science	7
Scopus	3
Elibrary	3
OpenAlex	9

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