Preparation of Enzyme-Activated Thapsigargin Prodrugs by Solid-Phase Synthesis

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Preparation of Enzyme-Activated Thapsigargin Prodrugs by Solid-Phase Synthesis. / Zimmermann, Tomas; Christensen, Søren Brøgger; Franzyk, Henrik.

I: Molecules, Bind 23, Nr. 6, 1463, 15.06.2018.

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Harvard

Zimmermann, T, Christensen, SB & Franzyk, H 2018, 'Preparation of Enzyme-Activated Thapsigargin Prodrugs by Solid-Phase Synthesis', Molecules, bind 23, nr. 6, 1463. https://doi.org/10.3390/molecules23061463

APA

Zimmermann, T., Christensen, S. B., & Franzyk, H. (2018). Preparation of Enzyme-Activated Thapsigargin Prodrugs by Solid-Phase Synthesis. Molecules, 23(6), [1463]. https://doi.org/10.3390/molecules23061463

Vancouver

Zimmermann T, Christensen SB, Franzyk H. Preparation of Enzyme-Activated Thapsigargin Prodrugs by Solid-Phase Synthesis. Molecules. 2018 jun. 15;23(6). 1463. https://doi.org/10.3390/molecules23061463

Author

Zimmermann, Tomas ; Christensen, Søren Brøgger ; Franzyk, Henrik. / Preparation of Enzyme-Activated Thapsigargin Prodrugs by Solid-Phase Synthesis. I: Molecules. 2018 ; Bind 23, Nr. 6.

Bibtex

@article{83cf35793b6e43d3bc8957eeeaf53fb0,
title = "Preparation of Enzyme-Activated Thapsigargin Prodrugs by Solid-Phase Synthesis",
abstract = "Since cells in solid tumors divide less rapidly than cells in the bone marrow or cells of theimmune system, mitotic inhibitors often cause severe side effects when used for treatment of diseaseslike prostate cancer and breast cancer. One approach to overcome this problem involves attemptsat developing drugs based on general cytotoxins, like calicheamicin and thapsigargin, which killcells at all phases of the cell cycle. However, such toxins can only be used when efficient targetingto the malignant tissue is possible. In the case of thapsigargin, selectivity for tumor-associated cellsis achieved by conjugating the drug to a peptide that is only cleaved in the vicinity of tumors torelease the cytotoxic drug or an analog with retained activity. Solid-phase synthesis protocols weredeveloped for preparation of three already validated prodrugs of thapsigargin: one prodrug cleavableby human kallikrein 2, one prodrug cleavable by prostate-specific antigen, and one prodrug cleavableby prostate-specific membrane antigen.",
keywords = "Former Faculty of Pharmaceutical Sciences, Prodrugs, targeted chemotherapy, Thapsigargin, Mipsagargin, solid-phase peptide synthesis, Cytotoxin-peptide conjugation",
author = "Tomas Zimmermann and Christensen, {S{\o}ren Br{\o}gger} and Henrik Franzyk",
year = "2018",
month = jun,
day = "15",
doi = "10.3390/molecules23061463",
language = "English",
volume = "23",
journal = "Molecules",
issn = "1420-3049",
publisher = "M D P I AG",
number = "6",

}

RIS

TY - JOUR

T1 - Preparation of Enzyme-Activated Thapsigargin Prodrugs by Solid-Phase Synthesis

AU - Zimmermann, Tomas

AU - Christensen, Søren Brøgger

AU - Franzyk, Henrik

PY - 2018/6/15

Y1 - 2018/6/15

N2 - Since cells in solid tumors divide less rapidly than cells in the bone marrow or cells of theimmune system, mitotic inhibitors often cause severe side effects when used for treatment of diseaseslike prostate cancer and breast cancer. One approach to overcome this problem involves attemptsat developing drugs based on general cytotoxins, like calicheamicin and thapsigargin, which killcells at all phases of the cell cycle. However, such toxins can only be used when efficient targetingto the malignant tissue is possible. In the case of thapsigargin, selectivity for tumor-associated cellsis achieved by conjugating the drug to a peptide that is only cleaved in the vicinity of tumors torelease the cytotoxic drug or an analog with retained activity. Solid-phase synthesis protocols weredeveloped for preparation of three already validated prodrugs of thapsigargin: one prodrug cleavableby human kallikrein 2, one prodrug cleavable by prostate-specific antigen, and one prodrug cleavableby prostate-specific membrane antigen.

AB - Since cells in solid tumors divide less rapidly than cells in the bone marrow or cells of theimmune system, mitotic inhibitors often cause severe side effects when used for treatment of diseaseslike prostate cancer and breast cancer. One approach to overcome this problem involves attemptsat developing drugs based on general cytotoxins, like calicheamicin and thapsigargin, which killcells at all phases of the cell cycle. However, such toxins can only be used when efficient targetingto the malignant tissue is possible. In the case of thapsigargin, selectivity for tumor-associated cellsis achieved by conjugating the drug to a peptide that is only cleaved in the vicinity of tumors torelease the cytotoxic drug or an analog with retained activity. Solid-phase synthesis protocols weredeveloped for preparation of three already validated prodrugs of thapsigargin: one prodrug cleavableby human kallikrein 2, one prodrug cleavable by prostate-specific antigen, and one prodrug cleavableby prostate-specific membrane antigen.

KW - Former Faculty of Pharmaceutical Sciences

KW - Prodrugs

KW - targeted chemotherapy

KW - Thapsigargin

KW - Mipsagargin

KW - solid-phase peptide synthesis

KW - Cytotoxin-peptide conjugation

U2 - 10.3390/molecules23061463

DO - 10.3390/molecules23061463

M3 - Journal article

C2 - 29914143

VL - 23

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 6

M1 - 1463

ER -

ID: 198571585