TY - JOUR AU - Zambra, Marco AU - Randelovic, Ivan AU - Talarico, Francesco AU - Borbély, Adina Noémi AU - Svajda, Laura AU - Tóvári, József AU - Mező, Gábor AU - Bodero, Lizeth AU - Colombo, Sveva AU - Arrigoni, Federico AU - Fasola, Elettra AU - Gazzola, Silvia AU - Piarulli, Umberto TI - Optimizing the enzymatic release of MMAE from isoDGR-based small molecule drug conjugate by incorporation of a GPLG-PABC enzymatically cleavable linker JF - FRONTIERS IN PHARMACOLOGY J2 - FRONT PHARMACOL VL - 14 PY - 2023 PG - 12 SN - 1663-9812 DO - 10.3389/fphar.2023.1215694 UR - https://m2.mtmt.hu/api/publication/34082424 ID - 34082424 N1 - Science and High Technology Department, University of Insubria, Como, Italy The National Tumor Biology Laboratory, Department of Experimental Pharmacology, National Institute of Oncology, Budapest, Hungary MTA-ELTE Lendület Ion Mobility Mass Spectrometry Research Group and Faculty of Science, Institute of Chemistry, ELTE Eötvös Loránd University, Budapest, Hungary KINETO Lab Ltd, Budapest, Hungary Doctoral School of Pathological Sciences, Semmelweis University, Budapest, Hungary ELKH-ELTE Research Group of Peptide Chemistry, Faculty of Science, Eötvös Loránd University, Budapest, Hungary Faculty of Science, Institute of Chemistry, Eötvös Loránd University, Budapest, Hungary Department of Chemistry Organic and Bioorganic Chemistry, Bielefeld University, Bielefeld, Germany Export Date: 29 August 2023 Correspondence Address: Gazzola, S.; Science and High Technology Department, Italy; email: s.gazzola@uninsubria.it Correspondence Address: Piarulli, U.; Science and High Technology Department, Italy; email: umberto.piarulli@uninsubria.it AB - Antibody-Drug Conjugates (ADCs) and Small Molecule-Drug Conjugates (SMDCs) represent successful examples of targeted drug-delivery technologies for overcoming unwanted side effects of conventional chemotherapy in cancer treatment. In both strategies, a cytotoxic payload is connected to the tumor homing moiety through a linker that releases the drug inside or in proximity of the tumor cell, and that represents a key component for the final therapeutic effect of the conjugate. Here, we show that the replacement of the Val-Ala- p -aminobenzyloxycarbamate linker with the Gly-Pro-Leu-Gly- p -aminobenzyloxycarbamate (GPLG-PABC) sequence as enzymatically cleavable linker in the SMDC bearing the cyclo [DKP -iso DGR] α V β 3 integrin ligand as tumor homing moiety and the monomethyl auristatin E (MMAE) as cytotoxic payload led to a 4-fold more potent anti-tumoral effect of the final conjugate on different cancer cell lines. In addition, the synthesized conjugate resulted to be significantly more potent than the free MMAE when tested following the “kiss-and-run” protocol, and the relative potency were clearly consistent with the expression of the α V β 3 integrin receptor in the considered cancer cell lines. In vitro enzymatic cleavage tests showed that the GPLG-PABC linker is cleaved by lysosomal enzymes, and that the released drug is observable already after 15 min of incubation. Although additional data are needed to fully characterize the releasing capacity of GPLG-PABC linker, our findings are of therapeutic significance since we are introducing an alternative to other well-established enzymatically sensitive peptide sequences that might be used in the future for generating more efficient and less toxic drug delivery systems. LA - English DB - MTMT ER - TY - JOUR AU - Nagy-Fazekas, Dóra AU - Stráner, Pál AU - Ecsédi, Péter AU - Taricska, Nóra AU - Borbély, Adina Noémi AU - Nyitray, László AU - Perczel, András TI - A Novel Fusion Protein System for the Production of Nanobodies and the SARS-CoV-2 Spike RBD in a Bacterial System JF - BIOENGINEERING J2 - BIOENGINEERING-BASEL VL - 10 PY - 2023 IS - 3 SN - 2306-5354 DO - 10.3390/bioengineering10030389 UR - https://m2.mtmt.hu/api/publication/33715979 ID - 33715979 AB - Antibodies are key proteins of the immune system, and they are widely used for both research and theragnostic applications. Among them, camelid immunoglobulins (IgG) differ from the canonical human IgG molecules, as their light chains are completely missing; thus, they have only variable domains on their heavy chains (VHHs). A single VHH domain, often called a nanobody, has favorable structural, biophysical, and functional features compared to canonical antibodies. Therefore, robust and efficient production protocols relying on recombinant technologies are in high demand. Here, by utilizing ecotin, an Escherichia coli protein, as a fusion partner, we present a bacterial expression system that allows an easy, fast, and cost-effective way to prepare nanobodies. Ecotin was used here as a periplasmic translocator and a passive refolding chaperone, which allowed us to reach high-yield production of nanobodies. We also present a new, easily applicable prokaryotic expression and purification method of the receptor-binding domain (RBD) of the SARS-CoV-2 S protein for interaction assays. We demonstrate using ECD spectroscopy that the bacterially produced RBD is well-folded. The bacterially produced nanobody was shown to bind strongly to the recombinant RBD, with a Kd of 10 nM. The simple methods presented here could facilitate rapid interaction measurements in the event of the appearance of additional SARS-CoV-2 variants. LA - English DB - MTMT ER - TY - JOUR AU - Vári, Balázs AU - Dókus, Endre Levente AU - Borbély, Adina Noémi AU - Gaál, Anikó AU - Mező, Diána AU - Randelovic, Ivan AU - Sólyom-Tisza, Anna AU - Varga, Zoltán AU - Szoboszlai, Norbert AU - Mező, Gábor AU - Tóvári, József TI - SREKA-targeted liposomes for highly metastatic breast cancer therapy JF - DRUG DELIVERY : JOURNAL OF DELIVERY AND TARGETING OF THERAPEUTIC AGENTS J2 - DRUG DELIV VL - 30 PY - 2023 IS - 1 PG - 16 SN - 1071-7544 DO - 10.1080/10717544.2023.2174210 UR - https://m2.mtmt.hu/api/publication/33631672 ID - 33631672 N1 - National Institute of Oncology, Department of Experimental Pharmacology, National Tumor Biology Laboratory, Budapest, Hungary School of Ph.D. Studies, Semmelweis University, Budapest, Hungary Research Group of Peptide Chemistry, Eötvös Loránd Research Network, Budapest, Hungary Faculty of Science, Institute of Chemistry, Eötvös Loránd University, Budapest, Hungary MTA-ELTE Lendület Ion Mobility Mass Spectrometry Research Group, Budapest, Hungary Eötvös, Loránd Research Network, Research Centre for Natural Sciences, Institute of Materials and Environmental Chemistry, Biological Nanochemistry Research Group, Budapest, Hungary Department of Tumor Biology, National Korányi Institute of Pulmonology, Budapest, Hungary Export Date: 3 November 2023 CODEN: DDELE Correspondence Address: Tóvári, J.; National Institute of Oncology, Hungary; email: tovari.jozsef@oncol.hu Correspondence Address: Mező, G.; School of Ph.D. Studies, Hungary; email: gabor.mezo@ttk.elte.hu LA - English DB - MTMT ER - TY - JOUR AU - Gomena, Jacopo AU - Vári, Balázs AU - Szabó, Rita (Oláhné) AU - Biri-Kovács, Beáta AU - Bősze, Szilvia AU - Borbély, Adina Noémi AU - Soós, Ádám AU - Randelovic, Ivan AU - Tóvári, József AU - Mező, Gábor TI - Targeting the Gastrin-Releasing Peptide Receptor (GRP-R) in Cancer Therapy: Development of Bombesin-Based Peptide–Drug Conjugates. Development of Bombesin-Based Peptide-Drug Conjugates. TS - Development of Bombesin-Based Peptide-Drug Conjugates. JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 4 PG - 21 SN - 1661-6596 DO - 10.3390/ijms24043400 UR - https://m2.mtmt.hu/api/publication/33631637 ID - 33631637 N1 - Institute of Chemistry, Faculty of Science, Eötvös Loránd University, Budapest, 1117, Hungary ELKH-ELTE Research Group of Peptide Chemistry, Budapest, 1117, Hungary Department of Experimental Pharmacology, National Institute of Oncology, Budapest, 1122, Hungary Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, 1089, Hungary MTA-ELTE Lendület Ion Mobility Mass Spectrometry Research Group, Budapest, 1117, Hungary Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, 1085, Hungary KINETO Lab Ltd., Budapest, 1037, Hungary Export Date: 11 July 2023 Correspondence Address: Mező, G.; Institute of Chemistry, Hungary; email: gabor.mezo@ttk.elte.hu AB - Targeted tumour therapy has proved to be an efficient alternative to overcome the limitations of conventional chemotherapy. Among several receptors upregulated in cancer cells, the gastrin-releasing peptide receptor (GRP-R) has recently emerged as a promising target for cancer imaging, diagnosing and treatment due to its overexpression on cancerous tissues such as breast, prostate, pancreatic and small-cell lung cancer. Herein, we report on the in vitro and in vivo selective delivery of the cytotoxic drug daunorubicin to prostate and breast cancer, by targeting GRP-R. Exploiting many bombesin analogues as homing peptides, including a newly developed peptide, we produced eleven daunorubicin-containing peptide–drug conjugates (PDCs), acting as drug delivery systems to safely reach the tumour environment. Two of our bioconjugates revealed remarkable anti-proliferative activity, an efficient uptake by all three tested human breast and prostate cancer cell lines, high stability in plasma and a prompt release of the drug-containing metabolite by lysosomal enzymes. Moreover, they revealed a safe profile and a consistent reduction of the tumour volume in vivo. In conclusion, we highlight the importance of GRP-R binding PDCs in targeted cancer therapy, with the possibility of further tailoring and optimisation. LA - English DB - MTMT ER - TY - GEN AU - Vári, Balázs AU - Dókus, Endre Levente AU - Borbély, Adina Noémi AU - Gaál, Anikó AU - Mező, Diána AU - Randelovic, Ivan AU - Szoboszlai, Norbert AU - Mező, Gábor AU - Tóvári, József TI - PEGylated liposomes in targeted cancer therapy using SREKA as targeting moiety PY - 2022 UR - https://m2.mtmt.hu/api/publication/33718828 ID - 33718828 N1 - poster LA - English DB - MTMT ER - TY - JOUR AU - Czuczi, Tamás AU - Murányi, József AU - Bárány, Péter Tibor AU - Móra , István András AU - Borbély, Adina Noémi AU - Csala, Miklós AU - Csámpai, Antal TI - Synthesis and Antiproliferative Activity of Novel Imipridone–Ferrocene Hybrids with Triazole and Alkyne Linkers JF - PHARMACEUTICALS J2 - PHARMACEUTICALS-BASE VL - 15 PY - 2022 IS - 4 PG - 19 SN - 1424-8247 DO - 10.3390/ph15040468 UR - https://m2.mtmt.hu/api/publication/32782717 ID - 32782717 LA - English DB - MTMT ER - TY - JOUR AU - Virág, Dávid AU - Kremmer, Tibor AU - Lőrincz, Kende Kálmán AU - Kiss, Norbert AU - Jobbágy, Antal AU - Bozsányi, Szabolcs AU - Gulyás, Lili AU - Wikonkál, Norbert AU - Schlosser, Gitta (Vácziné) AU - Borbély, Adina Noémi AU - Huba, Zsófia AU - Dalmadiné Kiss, Borbála AU - Antal, István AU - Ludányi, Krisztina TI - Altered Glycosylation of Human Alpha-1-Acid Glycoprotein as a Biomarker for Malignant Melanoma JF - MOLECULES J2 - MOLECULES VL - 26 PY - 2021 IS - 19 PG - 12 SN - 1420-3049 DO - 10.3390/molecules26196003 UR - https://m2.mtmt.hu/api/publication/32288001 ID - 32288001 N1 - Department of Pharmaceutics, Semmelweis University, Hőgyes Endre utca 7, Budapest, H-1092, Hungary Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, Mária utca. 41, Budapest, H-1085, Hungary MTA-ELTE Lendület Ion Mobility Mass Spectrometry Research Group, Institute of Chemistry, Faculty of Science, ELTE Eötvös Loránd University, Pázmány Péter sétány 1/A, Budapest, H-1117, Hungary Cited By :1 Export Date: 18 July 2022 CODEN: MOLEF Correspondence Address: Ludányi, K.; Department of Pharmaceutics, Hőgyes Endre utca 7, Hungary; email: ludanyi.krisztina@pharma.semmelweis-univ.hu LA - English DB - MTMT ER - TY - JOUR AU - Borbély, Adina Noémi AU - Pethő, Lilla AU - Szabó, Ildikó AU - Almajidi, Mohammed AU - Steckel, Arnold AU - Nagy, Tibor AU - Kéki, Sándor AU - Kalló, Gergő AU - Csősz, Éva AU - Mező, Gábor AU - Schlosser, Gitta (Vácziné) TI - Structural Characterization of Daunomycin-Peptide Conjugates by Various Tandem Mass Spectrometric Techniques JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 22 PY - 2021 IS - 4 SN - 1661-6596 DO - 10.3390/ijms22041648 UR - https://m2.mtmt.hu/api/publication/31855083 ID - 31855083 N1 - MTA-ELTE Lendület Ion Mobility Mass Spectrometry Research Group and Department of Analytical Chemistry, ELTE Eötvös Loránd University, Pázmány Péter sétány 1/A, Budapest, H-1117, Hungary Eötvös Loránd Research Network, Supported Research Groups, Research Group of Peptide Chemistry, Pázmány Péter sétány 1/A, Budapest, H-1117, Hungary Hevesy György PhD School of Chemistry, ELTE Eötvös Loránd University, Pázmány Péter sétány 1/A, Budapest, H-1117, Hungary Department of Applied Chemistry, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, Debrecen, H-4032, Hungary Proteomics Core Facility, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Egyetem tér 1, Debrecen, H-4032, Hungary Department of Organic Chemistry, ELTE Eötvös Loránd University, Pázmány Péter sétány 1/A, Budapest, H-1117, Hungary Export Date: 31 January 2023 Correspondence Address: Schlosser, G.; MTA-ELTE Lendület Ion Mobility Mass Spectrometry Research Group and Department of Analytical Chemistry, Pázmány Péter sétány 1/A, Hungary; email: schlosser@caesar.elte.hu LA - English DB - MTMT ER - TY - CHAP AU - Schlosser, Gitta (Vácziné) AU - Al-Majidi, M. AU - Borbély, Adina Noémi AU - Pethő, Lilla AU - Szabó, Dániel AU - Dókus, Endre Levente AU - Mező, Gábor ED - Mező, Gábor TI - Tandem mass spectrometry of daunorubicin-containing peptide conjugates T2 - Development of bioconjugates and their module constructs for targeted therapy of cancers with high mortality PB - Eötvös Loránd Tudományegyetem (ELTE) CY - Budapest SN - 9789634892861 PY - 2020 SP - 55 EP - 59 PG - 5 UR - https://m2.mtmt.hu/api/publication/31917020 ID - 31917020 LA - English DB - MTMT ER - TY - JOUR AU - Anselmi, Michele AU - Borbély, Adina Noémi AU - Figueras, Eduard AU - Michalek, Carmela AU - Kemker, Isabell AU - Gentilucci, Luca AU - Sewald, Norbert TI - Linker Hydrophilicity Modulates the Anticancer Activity of RGD–Cryptophycin Conjugates JF - CHEMISTRY-A EUROPEAN JOURNAL J2 - CHEM-EUR J VL - 27 PY - 2020 IS - 3 SP - 1015 EP - 1022 PG - 8 SN - 0947-6539 DO - 10.1002/chem.202003471 UR - https://m2.mtmt.hu/api/publication/31856717 ID - 31856717 LA - English DB - MTMT ER -