Protein modification by thiolactone homocysteine chemistry: a multifunctionalized human serum albumin theranostic

Protein modification by thiolactone homocysteine chemistry: a multifunctionalized human serum albumin theranostic Full article

Journal

RSC Medicinal Chemistry
, E-ISSN: 2632-8682

Output data

Year: 2020, Volume: 11, Number: 11, Pages: 1314-1325 Pages count : 12 DOI: 10.1039/c9md00516a

Authors

Popova Tatyana ^1,2 , Krumkacheva Olesya A. ^2,3 , Burmakova Anna S. ^1,2 , Spitsyna Anna S. ^2,4 , Zakharova Olga D. ¹ , Lisitskiy Vladimir A. ¹ , Kirilyuk Igor A. ⁴ , Silnikov Vladimir N. ¹ , Bowman Michael K. ^4,5 , Bagryanskaya Elena G. ^2,4 , Godovikova Tatyana S. ¹

Affiliations

1	Institute of Chemical Biology and Fundamental Medicine, SB RAS, 630090 Novosibirsk, Russia
2	Novosibirsk State University, 630090 Novosibirsk, Russia
3	International Tomography Center, SB RAS, 630090 Novosibirsk, Russia
4	Novosibirsk Institute of Organic Chemistry, SB RAS, 630090 Novosibirsk, Russia
5	University of Alabama, Tuscaloosa, Alabama 35487-0336, USA

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.

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

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