Protein modification by thiolactone homocysteine chemistry

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Protein modification by thiolactone homocysteine chemistry : A multifunctionalized human serum albumin theranostic. / Popova, Tatyana V.; Krumkacheva, Olesya A.; Burmakova, Anna S. et al.

In: RSC Medicinal Chemistry, Vol. 11, No. 11, 02.04.2020, p. 1314-1325.

Research output: Contribution to journal › Article › peer-review

BibTeX

@article{d460d0eb1d964d0bac761f8579b0d0b9,

title = "Protein modification by thiolactone homocysteine chemistry: A multifunctionalized human serum albumin theranostic",

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 ERα in our experiments. These results provide further impetus to develop a serum protein for delivery of tamoxifen to cancer cells. ",

keywords = "IN-VIVO, FC-RECEPTOR, SPIN-LABEL, HALF-LIFE, CONFORMATIONAL-CHANGES, FUNCTIONAL IMPAIRMENT, VERSATILE PLATFORM, CLICK CHEMISTRY, DRUG-DELIVERY, TAMOXIFEN",

author = "Popova, {Tatyana V.} and Krumkacheva, {Olesya A.} and Burmakova, {Anna S.} and Spitsyna, {Anna S.} and Zakharova, {Olga D.} and Lisitskiy, {Vladimir A.} and Kirilyuk, {Igor A.} and Silnikov, {Vladimir N.} and Bowman, {Michael K.} and Bagryanskaya, {Elena G.} and Godovikova, {Tatyana S.}",

year = "2020",

month = apr,

day = "2",

doi = "10.1039/c9md00516a",

language = "English",

volume = "11",

pages = "1314--1325",

journal = "RSC Medicinal Chemistry",

issn = "2632-8682",

publisher = "Royal Society of Chemistry",

number = "11",

}

RIS

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.

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

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

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