Missing Selectivity of Targeted 4β-Phorbol Prodrugs Expected to be Potential Chemotherapeutics

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Standard

Missing Selectivity of Targeted 4β-Phorbol Prodrugs Expected to be Potential Chemotherapeutics. / Tarvainen, Ilari; Zimmermann, Tomas; Heinonen, Pia; Jäntti, Maria Helena ; Yli-Kauhaluoma, Jari; Talman, Virpi; Franzyk, Henrik; Tuominen, Raimo K; Christensen, Søren Brøgger.

I: A C S Medicinal Chemistry Letters, Bind 11, Nr. 5, 2020, s. 671-677.

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Harvard

Tarvainen, I, Zimmermann, T, Heinonen, P, Jäntti, MH, Yli-Kauhaluoma, J, Talman, V, Franzyk, H, Tuominen, RK & Christensen, SB 2020, 'Missing Selectivity of Targeted 4β-Phorbol Prodrugs Expected to be Potential Chemotherapeutics', A C S Medicinal Chemistry Letters, bind 11, nr. 5, s. 671-677. https://doi.org/10.1021/acsmedchemlett.9b00554

APA

Tarvainen, I., Zimmermann, T., Heinonen, P., Jäntti, M. H., Yli-Kauhaluoma, J., Talman, V., Franzyk, H., Tuominen, R. K., & Christensen, S. B. (2020). Missing Selectivity of Targeted 4β-Phorbol Prodrugs Expected to be Potential Chemotherapeutics. A C S Medicinal Chemistry Letters, 11(5), 671-677. https://doi.org/10.1021/acsmedchemlett.9b00554

Vancouver

Tarvainen I, Zimmermann T, Heinonen P, Jäntti MH, Yli-Kauhaluoma J, Talman V o.a. Missing Selectivity of Targeted 4β-Phorbol Prodrugs Expected to be Potential Chemotherapeutics. A C S Medicinal Chemistry Letters. 2020;11(5):671-677. https://doi.org/10.1021/acsmedchemlett.9b00554

Author

Tarvainen, Ilari ; Zimmermann, Tomas ; Heinonen, Pia ; Jäntti, Maria Helena ; Yli-Kauhaluoma, Jari ; Talman, Virpi ; Franzyk, Henrik ; Tuominen, Raimo K ; Christensen, Søren Brøgger. / Missing Selectivity of Targeted 4β-Phorbol Prodrugs Expected to be Potential Chemotherapeutics. I: A C S Medicinal Chemistry Letters. 2020 ; Bind 11, Nr. 5. s. 671-677.

Bibtex

@article{daf52a1323024894bcf8b0f0cea20a9c,
title = "Missing Selectivity of Targeted 4β-Phorbol Prodrugs Expected to be Potential Chemotherapeutics",
abstract = "Targeting cytotoxic 4β-phorbol esters toward cancer tissue was attempted by conjugating a 4β-pborbol derivative with substrates for the proteases prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) expressed in cancer tissue. The hydrophilic peptide moiety was hypothesized to prevent penetration of the prodrugs into cells and prevent interaction with PKC. Cleavage of the peptide in cancer tumors was envisioned to release lipophilic cytotoxins, which subsequently penetrate into cancer cells. The 4β-phorbol esters were prepared from 4β-phorbol isolated from Croton tiglium seeds, while the peptides were prepared by solid-phase synthesis. Cellular assays revealed activation of PKC by the prodrugs and efficient killing of both peptidase positive as well as peptidase negative cells. Consequently no selectivity for enzyme expressing cells was found.",
keywords = "Faculty of Health and Medical Sciences, 4β-Phorbol ester, Protease-assisted targeting, Targeted chemotherapy, Prodrug, Prostate-specific antigen, Prostate-specific membrane antigen",
author = "Ilari Tarvainen and Tomas Zimmermann and Pia Heinonen and J{\"a}ntti, {Maria Helena} and Jari Yli-Kauhaluoma and Virpi Talman and Henrik Franzyk and Tuominen, {Raimo K} and Christensen, {S{\o}ren Br{\o}gger}",
year = "2020",
doi = "10.1021/acsmedchemlett.9b00554",
language = "English",
volume = "11",
pages = "671--677",
journal = "ACS Medicinal Chemistry Letters",
issn = "1948-5875",
publisher = "American Chemical Society",
number = "5",

}

RIS

TY - JOUR

T1 - Missing Selectivity of Targeted 4β-Phorbol Prodrugs Expected to be Potential Chemotherapeutics

AU - Tarvainen, Ilari

AU - Zimmermann, Tomas

AU - Heinonen, Pia

AU - Jäntti, Maria Helena

AU - Yli-Kauhaluoma, Jari

AU - Talman, Virpi

AU - Franzyk, Henrik

AU - Tuominen, Raimo K

AU - Christensen, Søren Brøgger

PY - 2020

Y1 - 2020

N2 - Targeting cytotoxic 4β-phorbol esters toward cancer tissue was attempted by conjugating a 4β-pborbol derivative with substrates for the proteases prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) expressed in cancer tissue. The hydrophilic peptide moiety was hypothesized to prevent penetration of the prodrugs into cells and prevent interaction with PKC. Cleavage of the peptide in cancer tumors was envisioned to release lipophilic cytotoxins, which subsequently penetrate into cancer cells. The 4β-phorbol esters were prepared from 4β-phorbol isolated from Croton tiglium seeds, while the peptides were prepared by solid-phase synthesis. Cellular assays revealed activation of PKC by the prodrugs and efficient killing of both peptidase positive as well as peptidase negative cells. Consequently no selectivity for enzyme expressing cells was found.

AB - Targeting cytotoxic 4β-phorbol esters toward cancer tissue was attempted by conjugating a 4β-pborbol derivative with substrates for the proteases prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) expressed in cancer tissue. The hydrophilic peptide moiety was hypothesized to prevent penetration of the prodrugs into cells and prevent interaction with PKC. Cleavage of the peptide in cancer tumors was envisioned to release lipophilic cytotoxins, which subsequently penetrate into cancer cells. The 4β-phorbol esters were prepared from 4β-phorbol isolated from Croton tiglium seeds, while the peptides were prepared by solid-phase synthesis. Cellular assays revealed activation of PKC by the prodrugs and efficient killing of both peptidase positive as well as peptidase negative cells. Consequently no selectivity for enzyme expressing cells was found.

KW - Faculty of Health and Medical Sciences

KW - 4β-Phorbol ester

KW - Protease-assisted targeting

KW - Targeted chemotherapy

KW - Prodrug

KW - Prostate-specific antigen

KW - Prostate-specific membrane antigen

U2 - 10.1021/acsmedchemlett.9b00554

DO - 10.1021/acsmedchemlett.9b00554

M3 - Journal article

C2 - 32435369

VL - 11

SP - 671

EP - 677

JO - ACS Medicinal Chemistry Letters

JF - ACS Medicinal Chemistry Letters

SN - 1948-5875

IS - 5

ER -

ID: 232592750