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Novel Peptide–Drug Conjugates with Dual Anticancer Activity. / O’Flaherty, Siobhán; Luzina, Olga A.; Dyrkheeva, Nadezhda S. et al.

In: International Journal of Molecular Sciences, Vol. 25, No. 22, 12411, 11.2024.

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

Harvard

O’Flaherty, S, Luzina, OA, Dyrkheeva, NS, Krier, Y, Leprince, J, Zakharenko, AL, Pokrovsky, MA, Pokrovsky, AG, Lavrik, OI, Salakhutdinov, NF, Varbanov, M, Devocelle, M & Volcho, KP 2024, 'Novel Peptide–Drug Conjugates with Dual Anticancer Activity', International Journal of Molecular Sciences, vol. 25, no. 22, 12411. https://doi.org/10.3390/ijms252212411

APA

O’Flaherty, S., Luzina, O. A., Dyrkheeva, N. S., Krier, Y., Leprince, J., Zakharenko, A. L., Pokrovsky, M. A., Pokrovsky, A. G., Lavrik, O. I., Salakhutdinov, N. F., Varbanov, M., Devocelle, M., & Volcho, K. P. (2024). Novel Peptide–Drug Conjugates with Dual Anticancer Activity. International Journal of Molecular Sciences, 25(22), [12411]. https://doi.org/10.3390/ijms252212411

Vancouver

O’Flaherty S, Luzina OA, Dyrkheeva NS, Krier Y, Leprince J, Zakharenko AL et al. Novel Peptide–Drug Conjugates with Dual Anticancer Activity. International Journal of Molecular Sciences. 2024 Nov;25(22):12411. doi: 10.3390/ijms252212411

Author

O’Flaherty, Siobhán ; Luzina, Olga A. ; Dyrkheeva, Nadezhda S. et al. / Novel Peptide–Drug Conjugates with Dual Anticancer Activity. In: International Journal of Molecular Sciences. 2024 ; Vol. 25, No. 22.

BibTeX

@article{ce214d7841e74aecb1d570e9ec6cdb2a,
title = "Novel Peptide–Drug Conjugates with Dual Anticancer Activity",
abstract = "Cationic antimicrobial peptides (AMPs), also called host defence peptides, have established antimicrobial and anticancer activities. Conjugation of an AMP to a bioactive molecule with complementary activity can address some of the clinical limitations of the peptide candidate. This approach has been particularly applied in antimicrobial applications of AMPs, but it remains relatively less explored in the generation of anticancer candidates. In this study, two usnic acid derivatives, based on hydrazinothiazole and benzylidenefuranone pharmacophore moieties, respectively, were conjugated to L-K6, a lysine/leucine-rich AMP, through a new pyrazole ligation intrinsically driven by the cargo molecule. Both components, the usnic acid derivative and the peptide, are selectively active against cancer cells, by targeting the human DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) and through DNA damage, respectively. The two conjugates, based on a hydrazone linkage, exhibited pleiotropic effects, ranging from reduction in the activity of the parent drugs to their conservation or even enhancement. Notably, the conjugates retained some anti-TDP1 activity and displayed intermediate, or even higher, cytotoxicities against glioblastoma cells, compared to their individual components.",
keywords = "anticancer, antimicrobial peptides, peptide–drug conjugates, secondary metabolites, usnic acid",
author = "Siobh{\'a}n O{\textquoteright}Flaherty and Luzina, {Olga A.} and Dyrkheeva, {Nadezhda S.} and Ysaline Krier and J{\'e}r{\^o}me Leprince and Zakharenko, {Alexandra L.} and Pokrovsky, {Mikhail A.} and Pokrovsky, {Andrey G.} and Lavrik, {Olga I.} and Salakhutdinov, {Nariman F.} and Mihayl Varbanov and Marc Devocelle and Volcho, {Konstantin P.}",
note = "The authors acknowledge the Erasmus+ Programme of the European Union for the mobility of researchers between RCSI and Novosibirsk State University, funded under Key Action 1 International Credit Mobility Programme, grant numbers 2015-2-IE02-KA107-000423 and 2018-1-IE02-KA107-000606, and between RCSI and the University of Lorraine under the Lifelong Learning Programme and Key Action 103. This publication stemmed from research conducted with the financial support of Science Foundation Ireland under grant number 12/RC/2275_P2. The authors also acknowledge a grant from the Ministry of Science and Higher Education of the Russian Federation (agreement No. 075-15-2024-536). For the purpose of open access, the authors have applied a CC BY public copyright licence to any author-accepted manuscript version arising from this submission.",
year = "2024",
month = nov,
doi = "10.3390/ijms252212411",
language = "English",
volume = "25",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "22",

}

RIS

TY - JOUR

T1 - Novel Peptide–Drug Conjugates with Dual Anticancer Activity

AU - O’Flaherty, Siobhán

AU - Luzina, Olga A.

AU - Dyrkheeva, Nadezhda S.

AU - Krier, Ysaline

AU - Leprince, Jérôme

AU - Zakharenko, Alexandra L.

AU - Pokrovsky, Mikhail A.

AU - Pokrovsky, Andrey G.

AU - Lavrik, Olga I.

AU - Salakhutdinov, Nariman F.

AU - Varbanov, Mihayl

AU - Devocelle, Marc

AU - Volcho, Konstantin P.

N1 - The authors acknowledge the Erasmus+ Programme of the European Union for the mobility of researchers between RCSI and Novosibirsk State University, funded under Key Action 1 International Credit Mobility Programme, grant numbers 2015-2-IE02-KA107-000423 and 2018-1-IE02-KA107-000606, and between RCSI and the University of Lorraine under the Lifelong Learning Programme and Key Action 103. This publication stemmed from research conducted with the financial support of Science Foundation Ireland under grant number 12/RC/2275_P2. The authors also acknowledge a grant from the Ministry of Science and Higher Education of the Russian Federation (agreement No. 075-15-2024-536). For the purpose of open access, the authors have applied a CC BY public copyright licence to any author-accepted manuscript version arising from this submission.

PY - 2024/11

Y1 - 2024/11

N2 - Cationic antimicrobial peptides (AMPs), also called host defence peptides, have established antimicrobial and anticancer activities. Conjugation of an AMP to a bioactive molecule with complementary activity can address some of the clinical limitations of the peptide candidate. This approach has been particularly applied in antimicrobial applications of AMPs, but it remains relatively less explored in the generation of anticancer candidates. In this study, two usnic acid derivatives, based on hydrazinothiazole and benzylidenefuranone pharmacophore moieties, respectively, were conjugated to L-K6, a lysine/leucine-rich AMP, through a new pyrazole ligation intrinsically driven by the cargo molecule. Both components, the usnic acid derivative and the peptide, are selectively active against cancer cells, by targeting the human DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) and through DNA damage, respectively. The two conjugates, based on a hydrazone linkage, exhibited pleiotropic effects, ranging from reduction in the activity of the parent drugs to their conservation or even enhancement. Notably, the conjugates retained some anti-TDP1 activity and displayed intermediate, or even higher, cytotoxicities against glioblastoma cells, compared to their individual components.

AB - Cationic antimicrobial peptides (AMPs), also called host defence peptides, have established antimicrobial and anticancer activities. Conjugation of an AMP to a bioactive molecule with complementary activity can address some of the clinical limitations of the peptide candidate. This approach has been particularly applied in antimicrobial applications of AMPs, but it remains relatively less explored in the generation of anticancer candidates. In this study, two usnic acid derivatives, based on hydrazinothiazole and benzylidenefuranone pharmacophore moieties, respectively, were conjugated to L-K6, a lysine/leucine-rich AMP, through a new pyrazole ligation intrinsically driven by the cargo molecule. Both components, the usnic acid derivative and the peptide, are selectively active against cancer cells, by targeting the human DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) and through DNA damage, respectively. The two conjugates, based on a hydrazone linkage, exhibited pleiotropic effects, ranging from reduction in the activity of the parent drugs to their conservation or even enhancement. Notably, the conjugates retained some anti-TDP1 activity and displayed intermediate, or even higher, cytotoxicities against glioblastoma cells, compared to their individual components.

KW - anticancer

KW - antimicrobial peptides

KW - peptide–drug conjugates

KW - secondary metabolites

KW - usnic acid

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85210558699&origin=inward&txGid=65cfeda73f0a36e3d0f68e9675c17e88

UR - https://www.mendeley.com/catalogue/cecc20a3-c274-30af-9dfd-563d6be14096/

U2 - 10.3390/ijms252212411

DO - 10.3390/ijms252212411

M3 - Article

C2 - 39596476

VL - 25

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 22

M1 - 12411

ER -

ID: 61146738