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Review

Oxime-Linked Peptide–Daunomycin Conjugates as Good Tools for Selection of Suitable Homing Devices in Targeted Tumor Therapy: An Overview

by
Gábor Mező
1,2,*,
Jacopo Gomena
1,2,
Ivan Ranđelović
3,
Endre Levente Dókus
1,
Krisztina Kiss
1,4,
Lilla Pethő
1,
Sabine Schuster
1,2,
Balázs Vári
3,5,
Diána Vári-Mező
1,3,5,
Eszter Lajkó
6,
Lívia Polgár
6,
László Kőhidai
6,
József Tóvári
3,5 and
Ildikó Szabó
1
1
HUN-REN-ELTE Research Group of Peptide Chemistry, 1117 Budapest, Hungary
2
Hevesy György PhD School of Chemistry, Eötvös Loránd University, 1117 Budapest, Hungary
3
Department of Experimental Pharmacology and the National Tumor Biology Laboratory, National Institute of Oncology, 1122 Budapest, Hungary
4
Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1111 Budapest, Hungary
5
School of Ph.D. Studies, Doctoral School of Pathological Sciences, Semmelweis University, 1085 Budapest, Hungary
6
Department of Genetics, Cell- and Immunobiology, Semmelweis University, 1089 Budapest, Hungary
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(3), 1864; https://doi.org/10.3390/ijms25031864
Submission received: 21 December 2023 / Revised: 29 January 2024 / Accepted: 31 January 2024 / Published: 3 February 2024
(This article belongs to the Special Issue The Role of Peptides and Peptide Syntheses in Cancer Therapy)
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Abstract

Chemotherapy is still one of the main therapeutic approaches in cancer therapy. Nevertheless, its poor selectivity causes severe toxic side effects that, together with the development of drug resistance in tumor cells, results in a limitation for its application. Tumor-targeted drug delivery is a possible choice to overcome these drawbacks. As well as monoclonal antibodies, peptides are promising targeting moieties for drug delivery. However, the development of peptide–drug conjugates (PDCs) is still a big challenge. The main reason is that the conjugates have to be stable in circulation, but the drug or its active metabolite should be released efficiently in the tumor cells. For this purpose, suitable linker systems are needed that connect the drug molecule with the homing peptide. The applied linker systems are commonly categorized as cleavable and non-cleavable linkers. Both the groups possess advantages and disadvantages that are summarized briefly in this manuscript. Moreover, in this review paper, we highlight the benefit of oxime-linked anthracycline–peptide conjugates in the development of PDCs. For instance, straightforward synthesis as well as a conjugation reaction proceed in excellent yields, and the autofluorescence of anthracyclines provides a good tool to select the appropriate homing peptides. Furthermore, we demonstrate that these conjugates can be used properly in in vivo studies. The results indicate that the oxime-linked PDCs are potential candidates for targeted tumor therapy.
Keywords: targeted tumor therapy; peptide–drug conjugates; homing peptides; daunomycin; oxime linkage; in vivo tumor growth inhibition targeted tumor therapy; peptide–drug conjugates; homing peptides; daunomycin; oxime linkage; in vivo tumor growth inhibition

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MDPI and ACS Style

Mező, G.; Gomena, J.; Ranđelović, I.; Dókus, E.L.; Kiss, K.; Pethő, L.; Schuster, S.; Vári, B.; Vári-Mező, D.; Lajkó, E.; et al. Oxime-Linked Peptide–Daunomycin Conjugates as Good Tools for Selection of Suitable Homing Devices in Targeted Tumor Therapy: An Overview. Int. J. Mol. Sci. 2024, 25, 1864. https://doi.org/10.3390/ijms25031864

AMA Style

Mező G, Gomena J, Ranđelović I, Dókus EL, Kiss K, Pethő L, Schuster S, Vári B, Vári-Mező D, Lajkó E, et al. Oxime-Linked Peptide–Daunomycin Conjugates as Good Tools for Selection of Suitable Homing Devices in Targeted Tumor Therapy: An Overview. International Journal of Molecular Sciences. 2024; 25(3):1864. https://doi.org/10.3390/ijms25031864

Chicago/Turabian Style

Mező, Gábor, Jacopo Gomena, Ivan Ranđelović, Endre Levente Dókus, Krisztina Kiss, Lilla Pethő, Sabine Schuster, Balázs Vári, Diána Vári-Mező, Eszter Lajkó, and et al. 2024. "Oxime-Linked Peptide–Daunomycin Conjugates as Good Tools for Selection of Suitable Homing Devices in Targeted Tumor Therapy: An Overview" International Journal of Molecular Sciences 25, no. 3: 1864. https://doi.org/10.3390/ijms25031864

APA Style

Mező, G., Gomena, J., Ranđelović, I., Dókus, E. L., Kiss, K., Pethő, L., Schuster, S., Vári, B., Vári-Mező, D., Lajkó, E., Polgár, L., Kőhidai, L., Tóvári, J., & Szabó, I. (2024). Oxime-Linked Peptide–Daunomycin Conjugates as Good Tools for Selection of Suitable Homing Devices in Targeted Tumor Therapy: An Overview. International Journal of Molecular Sciences, 25(3), 1864. https://doi.org/10.3390/ijms25031864

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