Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
Protein modification by thiolactone homocysteine chemistry : A multifunctionalized human serum albumin theranostic. / Popova, Tatyana V.; Krumkacheva, Olesya A.; Burmakova, Anna S. и др.
в: RSC Medicinal Chemistry, Том 11, № 11, 02.04.2020, стр. 1314-1325.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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TY - JOUR
T1 - Protein modification by thiolactone homocysteine chemistry
T2 - A multifunctionalized human serum albumin theranostic
AU - Popova, Tatyana V.
AU - Krumkacheva, Olesya A.
AU - Burmakova, Anna S.
AU - Spitsyna, Anna S.
AU - Zakharova, Olga D.
AU - Lisitskiy, Vladimir A.
AU - Kirilyuk, Igor A.
AU - Silnikov, Vladimir N.
AU - Bowman, Michael K.
AU - Bagryanskaya, Elena G.
AU - Godovikova, Tatyana S.
N1 - Publisher Copyright: © 2020 The Royal Society of Chemistry. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2020/4/2
Y1 - 2020/4/2
N2 - 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 ERα in our experiments. These results provide further impetus to develop a serum protein for delivery of tamoxifen to cancer cells.
AB - 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 ERα in our experiments. These results provide further impetus to develop a serum protein for delivery of tamoxifen to cancer cells.
KW - IN-VIVO
KW - FC-RECEPTOR
KW - SPIN-LABEL
KW - HALF-LIFE
KW - CONFORMATIONAL-CHANGES
KW - FUNCTIONAL IMPAIRMENT
KW - VERSATILE PLATFORM
KW - CLICK CHEMISTRY
KW - DRUG-DELIVERY
KW - TAMOXIFEN
UR - http://www.scopus.com/inward/record.url?scp=85096512911&partnerID=8YFLogxK
U2 - 10.1039/c9md00516a
DO - 10.1039/c9md00516a
M3 - Article
C2 - 34085043
AN - SCOPUS:85096512911
VL - 11
SP - 1314
EP - 1325
JO - RSC Medicinal Chemistry
JF - RSC Medicinal Chemistry
SN - 2632-8682
IS - 11
ER -
ID: 26134874