Development of bioconjugates for targeted tumor therapy of cancer types leading to high mortality  Page description

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Details of project

 
Identifier
119552
Type K
Principal investigator Mező, Gábor
Title in Hungarian Magas mortalitású daganatos megbetegedések irányított tumorterápiás kezelésére alkalmas biokonjugátumok fejlesztése
Title in English Development of bioconjugates for targeted tumor therapy of cancer types leading to high mortality
Keywords in Hungarian irányított tumorterápia, peptid hordozók. tumorellenes hatóanyagok, fág-könyvtárak, melanóma, tüdőrák, hasnyálmirigyrák, agytumorok
Keywords in English targeted tumor therapy, peptide carrier, anticancer drugs, phage display libraries, melanoma, lung cancer, pancreatic cancer, brain cancer
Discipline
Organic, Biomolecular, and Pharmaceutical Chemistry (Council of Physical Sciences)70 %
Ortelius classification: Pharmaceutical chemistry
Organic, Biomolecular, and Pharmaceutical Chemistry (Council of Physical Sciences)15 %
Cancer and its biological basis (Council of Medical and Biological Sciences)15 %
Panel Chemistry 2
Department or equivalent Institute of Chemistry (Eötvös Loránd University)
Participants Bánóczi, Zoltán
Biri-Kovács, Beáta
Bősze, Szilvia
Dókus, Endre Levente
Enyedi, Kata Nóra
Halmos, Gábor
Kapuvári, Bence
Kertész, István
Kóczán, György
Kőhalmy, Krisztina
Kőhidai, László
Lajkó, Eszter
Mező, Diána Tünde
Oláhné Szabó, Rita
Pethő, Lilla
Schlosser, Gitta Zsófia
Tóvári, József
Trencsényi, György
Várhegyi, Lea Sára
Vári, Balázs
Starting date 2016-10-01
Closing date 2022-09-30
Funding (in million HUF) 47.950
FTE (full time equivalent) 29.64
state running project





 

Final report

 
Results in Hungarian
A pályázat során célzott tumorterápiára alkalmas peptid – hatóanyag konjugátumokat szintetizáltunk (>100) és vizsgáltuk tumorellenes hatásukat in vitro és in vivo. Elsősorban a magas mortalitást okozó tumorokra (emlő, vastagbél, hasnyálmirigy, glioma, stb.) terveztünk olyan irányító peptideket, amelyek nagy szelektivitással a tumorsejtekbe juttatják a hatóanyagot megkímélve az egészséges szöveteket. Megállapítottuk, hogy az irányító peptidhez oxim-kötéssel kapcsolt daunomicin (Dau) kiváló rendszer az irányító peptidek szűrésére, mivel az oxim-kötés mind in vitro mind in vivo kísérletekben megfelelő stabilitással rendelkezik, és a Dau autofluoreszcens tulajdonsága miatt alkalmas a konjugátum sejtfelvételének vizsgálatára és a hatóanyag vagy annak metabolitjának a sejtbeni lokalizációjának meghatározására áramlási citométerrel és/vagy konfokális lézer mikroszkóp segítségével. A konjugátumok egereken történt in vivo tumornövekedés gátlása mellett vizsgáltuk azok krónikus és akut toxicitásukat és metasztázisra gyakorolt hatásukat. Megállapítottuk, hogy a konjugátumok minden esetben visszaszorították a hatóanyag toxikus mellékhatását és sokszor hatékonyabb tumorellene hatással rendelkeztek az alkalmazott dózisokban, mint a Dau a maximum tolerálható dózisban. Tehát lényegesen sikerült a terápiás ablak szélesítése a konjugátumok segítségével. Új hatékony tumorellenes szereket és hatékony formulázási módszereket is kidolgoztunk a biohasznosíthatóság érdekében (ld. a beszámolóban).
Results in English
In this project peptide – drug conjugates were prepared (>100) for targeted tumor therapy and their in vitro and in vivo antitumor effect was investigated. The homing peptides were developed mainly for tumor types causing high mortality (breast, colon, pancreatic cancers, glioma, etc.), that can target the drugs selectively and specifically to tumor cells sparing the healthy tumor tissues. It was indicated that the conjugates in which the daunomycin is attached to the homing peptides via oxime-linkage are suitable for selection of the most optimal structure of homing peptides. The reason is that the oxime bond is stable both in in vitro and in vivo experiments, furthermore the autofluorescence properties of Dau provides a good tool for the study of the cellular uptake and localization of the drug or its metabolite in the cells. These parameters were studied by flow cytometer and confocal laser microscopy. Next to the in vivo antitumor effect of the conjugates in mice, their chronic and acute toxicity and inhibition of metastases were also investigated. It was indicated the conjugates showed much less toxicity in all cases in comparison with the free drug at the maximum tolerated doses. Furthermore, the many of the conjugates were more active on tumor cells than the free drug. In this way we could increase the therapeutic windows of the applied drug. New antitumor drugs and efficient formulations were also developed for the improvement bioavailability (see in the summary).
Full text https://www.otka-palyazat.hu/download.php?type=zarobeszamolo&projektid=119552
Decision
Yes





 

List of publications

 
Sabine Schuster: Synthesis of GnRH and Somatostatin Cytotoxic Drug Conjugates, ELTE Doktori Iskola, 2019
Andrea Angello Pierluigi Tripodi: Development of a novel class of cyclic NGR peptides for targeted drug delivery, ELTE Doktori Iskola, 2020
Ivan Randelovic: Small molecule peptide-drug conjugates for targeted drug delivery in cancer therapy, Semmelweis Egyetem Doktori Iskola, 2021
Pethő Lilla: IRÁNYÍTOTT TUMORTERÁPIÁBAN ALKALMAZHATÓ HATÓANYAG-PEPTID KONJUGÁTUMOK HATÁSÁT BEFOLYÁSOLÓ TÉNYEZŐK VIZSGÁLATA, ELTE Doktori Iskola, 2019
Pethő L, OLáh-Szabó R, Mező G.: Influence of the Daunomycin Position on Bioactivity in Angiopep-2 - Drug Conjugates, 36th EPS Proceedings, 2022
Dókus LE, Lajkó E, Szász ZA, Vári-Mező D, Takács A, Kőhidai L, Mező G: Development of Pancreatic Tumor Specific Daunomycin – Peptide Conjugates Using Homing Peptides Selected by Phage Display Technique, 36th EPS Proceedings, 2022
Baranyai Z, Biri-Kovács B, Krátký M, Szeder B, Debreczeni ML, Budai J, Kovács B, Horváth L, Pári E, Németh Z, Cervenak L, Zsila F, Méhes E, Kiss É, Vinšová J, Bősze S.: Cellular Internalization and Inhibition Capacity of New Anti-Glioma Peptide Conjugates: Physicochemical Characterization and Evaluation on Various Monolayer- and 3D-Spheroid-Based in Vitro Platforms, J Med Chem 64: 2982-3005, 2021
Vári B, Dókus L, Borbély A, Gál A, Vári-Mező D, Randelovic I, Varga Z, Szoboszlai N, Mező G, Tóvári J: SREKA-targeted liposome for targeted therapy of highly metastatic cancers, Drug Delivery (submitted), 2022
Schuster S, Juhász É, Halmos G, Neundorf I, Gennari C, Mező G.: Development and biochemical characterization of self-immolative linker containing GnRH-III-drug conjugates., Int. J. Mol. Sci. 23, 5071, 2022
Kiss K, Hegedüs K, Vass P, Vári-Mező D, Farkas A, Nagy ZK, Molnár L, Tóvári J, Mező G, Marosi G.: Development of fast-dissolving dosage forms of curcuminoids by electrospinning for potential tumor therapy application., Int. J. Pharm. 611: 121327, 2022
Farkasinszky G, Dénes N, Rácz Sz, Kis A, Péliné Szabó J, Opposits G, Veres G, Balkay L, Kertész I, Mező G, Hunyadi J, Trencsényi Gy.: In vivo imaging of ischemia/reperfusion-mediated Aminopeptidase N expression in surgical rat model using 68Ga-NOTA-c(NGR)., IN VIVO 36: 657-666, 2022
Szabo JP, Denes N, Arato V, Racz S, Kis A, Opposits G, Kepes Z, Hajdu I, Joszai I, Emri M, Kertesz I, Mezo G, Trencsenyi G.: In Vivo Imaging of Neo-angiogenesis of Transplanted Metastases in Subrenal Capsule Assay Induced Rat Model, In Vivo 36: 1667-1675, 2022
Enyedi KN, Tóth S, Szakács G, Mező G: NGR-peptide-drug conjugates with dual targeting properties, PLOS ONE 12: (6) e0178632, 2017
Schuster S, Biri-Kovács B, Szeder B, Farkas V, Buday L, Szabó Z, Halmos G, Mező G.: Synthesis and in vitro biochemical evaluation of oxime bondlinked daunorubicin–GnRH-III conjugates developed for targeted drug delivery, Beilstein J Org Chem 14: 756-771, 2018
Tripodi AAP, Tóth S, Enyedi KN, Schlosser G, Szakács G, Mező G.: Development of novel cyclic NGR peptide–daunomycin conjugates with dual targeting property, Beilstein J Org Chem 14: 911-918, 2018
Vrettos EI, Mező G, Tzakos A.: On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site, Beilstein J Org Chem 14: 930-954, 2018
Polgár L, Lajkó E, Soós P, Láng O, Manea M, Merkely B, Mező G, Kőhidai L.: Drug targeting to decrease cardiotoxicity – determination of the cytotoxic effect of GnRH-based conjugates containing doxorubicin, daunorubicin and methotrexate on human, Beilstein J Org Chem 14: 1583-1594, 2018
Schuster S, Biri-Kovács B, Borbély A, Sewald N, Neundorf I, Gennari C, Mező G.: Synthesis and biochemical evaluation of GnRH-III-drug conjugates, J. Pept. Sci. SI. p. 79, 2018
Tripodi AAP, Tóth S, Randelovic I, Tóvári J, Mező G.: NGR-Dau conjugates a favorable tumor-homing motif with potential dual-targeting, J. Pept. Sci. SI. p. 162, 2018
Enyedi KN, Tripodi AAP, Mező G.: Biochemical-activity studies of NGR-peptide-drug conjugates for targeted tumour therapy, J. Pept. Sci. SI. p. 166-167, 2018
Pethő L, Murányi J, Kram N, Bökönyi G, Csík G, Mező G.: Synthesis and in vitro biological effect of GnRH-porphyrin IX conjugate, J. Pept. Sci. SI. p. 167, 2018
Adorján AE, Bősze S, Szabó I, Mező G.: Structure-activity relationship of HER2 receptor targeting peptide and its derivatives in targeted tumor therapy, J. Pept. Sci. SI. p. 167-168, 2018
Lajkó E, Spring S, Hegedüs R, Biri-Kovács B, Ingebrandt S, Mező G, Kőhidai L.: Comparative cell biological study of in vitro antitumor and antimetastatic activity on melanoma cells of GnRH-III-containing conjugates modified with short-chain fatty ac, Beilstein J Org Chem 14: 2495-2509, 2018
Schuster S, Biri-Kovács B, Szeder B, Farkas V, Buday L, Szabó Z, Halmos G, Mező G.: Synthesis and in vitro biochemical evaluation of oxime bondlinked daunorubicin–GnRH-III conjugates developed for targeted drug delivery, Beilstein J Org Chem 14: 756-771, 2018
Tripodi AAP, Tóth S, Enyedi KN, Schlosser G, Szakács G, Mező G.: Development of novel cyclic NGR peptide–daunomycin conjugates with dual targeting property, Beilstein J Org Chem 14: 911-918, 2018
Vrettos EI, Mező G, Tzakos A.: On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site, Beilstein J Org Chem 14: 930-954, 2018
Polgár L, Lajkó E, Soós P, Láng O, Manea M, Merkely B, Mező G, Kőhidai L.: Drug targeting to decrease cardiotoxicity – determination of the cytotoxic effect of GnRH-based conjugates containing doxorubicin, daunorubicin and methotrexate on human, Beilstein J Org Chem 14: 1583-1594, 2018
Schuster S, Biri-Kovács B, Borbély A, Sewald N, Neundorf I, Gennari C, Mező G.: Synthesis and biochemical evaluation of GnRH-III-drug conjugates, Proceedings of the 35th European Peptide Symposium, pp. 80-83, 2018
Tripodi AAP, Tóth S, Randelovic I, Tóvári J, Mező G.: NGR-Dau conjugates a favorable tumor-homing motif with potential dual-targeting, Proceedings of the 35th European Peptide Symposium, pp. 297-299, 2018
Enyedi KN, Tripodi AAP, Mező G.: Biochemical-activity studies of NGR-peptide-drug conjugates for targeted tumour therapy, Proceedings of the 35th European Peptide Symposium, pp. 315-316, 2018
Pethő L, Murányi J, Kram N, Bökönyi G, Csík G, Mező G.: Synthesis and in vitro biological effect of GnRH-porphyrin IX conjugate, Proceedings of the 35th European Peptide Symposium, pp. 317-319, 2018
Adorján AE, Bősze S, Szabó I, Mező G.: Structure-activity relationship of HER2 receptor targeting peptide and its derivatives in targeted tumor therapy, Proceedings of the 35th European Peptide Symposium, pp. 320-322, 2018
Lajkó E, Spring S, Hegedüs R, Biri-Kovács B, Ingebrandt S, Mező G, Kőhidai L.: Comparative cell biological study of in vitro antitumor and antimetastatic activity on melanoma cells of GnRH-III-containing conjugates modified with short-chain fatty ac, Beilstein J Org Chem 14: 2495-2509, 2018
Kiss K, Biri-Kovács B, Szabó R, Ranđelović I, Enyedi KN, Schlosser G, Orosz Á, Kapuvári B, Tóvári J, Mező G.: Sequence modification of heptapeptide selected by phage display as homing device for HT-29 colon cancer cells to improve the anti-tumour activity of drug delivery systems, Eur J Med Chem. 176:105-116., 2019
Pethő L, Mező G, Schlosser G.: Overcharging Effect in Electrospray Ionization Mass Spectra of Daunomycin-Tuftsin Bioconjugates., Molecules. 16;24(16), 2019
Lajkó E, Hegedüs R, Mező G, Kőhidai L.: Apoptotic Effects of Drug Targeting Conjugates Containing Different GnRH Analogs on Colon Carcinoma Cells., Int J Mol Sci. 20: 4421, 2019
Schuster S, Biri-Kovács B, Szeder B, Buday L, Gardi J, Szabó Z, Halmos G, Mező G.: Enhanced In Vitro Antitumor Activity of GnRH-III-Daunorubicin Bioconjugates Influenced by Sequence Modification., Pharmaceutics. 10(4):223., 2018
Randelovic I, Schuster S, Kapuvári B, Fossati G, Steinkühler C, Mező G, Tóvári J.: Improved In Vivo Anti-Tumor and Anti-Metastatic Effect of GnRH-III-Daunorubicin Analogs on Colorectal and Breast Carcinoma Bearing Mice, Int J Mol Sci. 20: 4763, 2019
Pethő L, Murányi J, Pénzes K, Gurbi B, Brauswetter D, Halmos G, Csík G, Mező G:: Suitability of GnRH Receptors for Targeted Photodynamic Therapy in Head and Neck Cancers., Int J Mol Sci, 20: 5027, 2019
Tripodi AAP, Randelovic I, Biri-Kovács B, Szeder B, Mező G, Tóvári J.: In vivo tumor growth inhibition and antiangiogenic effect of cyclic NGR peptide-daunomycin conjugates developed for targeted drug delivery, Pathology & Oncology Research, 2019
Tripodi AAP, Randelovic I, Biri-Kovács B, Szeder B, Mező G, Tóvári J.: In vivo tumor growth inhibition and antiangiogenic effect of cyclic NGR peptide-daunomycin conjugates developed for targeted drug delivery, Pathology & Oncology Research, 26(3): 1879-1892, 2020
Biri-Kovács B, Adorján A, Szabó I, Szeder B, Bősze S, Mező G.: Structure-activity relationship of HER2 receptor targeting peptide and its derivatives in targeted tumor therapy., Biomolecules 10(2): pii: E183., 2020
Pethő, L, Kasza G, Lajkó E, Láng O, Kőhidai L, Iván B, Mező G.: Amphiphilic drug-peptide-polymer conjugates based on poly(ethylene glycol) and hyperbranched polyglycerol for epidermal growth factor receptor targeting: the effect of th, Soft Matter 16: 5759-5769, 2020
Kiss K, Vass P, Farkas A, Hirsch E, Szabó E, Mező G, Nagy ZK, Marosi G.: A solid doxycycline HP-β-CD formulation for reconstitution (iv bolus) prepared by scaled-up electrospinning., Int J Pharm. 586: 119539, 2020
Dókus LE, Lajkó E, Randelovic I, Mező D, Schlosser G, Kőhidai L, Tóvári J, Mező G.: Phage Display-Based Homing Peptide-Daunomycin Conjugates for Selective Drug Targeting to PANC-1 Pancreatic Cancer., Pharmaceutics 12: 576, 2020
Al-Majidi M, Szabó D, Dókus L, Steckel A, Mező G, Schlosser G.: Energy‐resolved HCD fragmentation of daunorubicin‐peptide conjugates, J Mass Spectrom 55(10): e4641., 2020
Kis A, Dénes N, Szabó JP, Arató V, Jószai I, Enyedi KN, Lakatos Sz, Garai I, Mező G, Kertész I, Trencsényi Gy.: In vivo assessment of aminopeptidase N (APN/CD13) specificity of different 68Ga-labelled NGR derivatives using PET/MRI imaging., Int J Pharm. 589: 119881, 2020
Tripodi AAP, Randelovic I, Biri-Kovács B, Szeder B, Mező G, Tóvári J.: In vivo tumor growth inhibition and antiangiogenic effect of cyclic NGR peptide-daunomycin conjugates developed for targeted drug delivery, Pathology & Oncology Research, 26(3): 1879-1892, 2020
Biri-Kovács B, Adorján A, Szabó I, Szeder B, Bősze S, Mező G.: Structure-activity relationship of HER2 receptor targeting peptide and its derivatives in targeted tumor therapy., Biomolecules 10(2): pii: E183., 2020
Pethő, L, Kasza G, Lajkó E, Láng O, Kőhidai L, Iván B, Mező G.: Amphiphilic drug-peptide-polymer conjugates based on poly(ethylene glycol) and hyperbranched polyglycerol for epidermal growth factor receptor targeting: the effect of th, Soft Matter 16: 5759-5769, 2020
Kiss K, Vass P, Farkas A, Hirsch E, Szabó E, Mező G, Nagy ZK, Marosi G.: A solid doxycycline HP-β-CD formulation for reconstitution (iv bolus) prepared by scaled-up electrospinning., Int J Pharm. 586: 119539, 2020
Dókus LE, Lajkó E, Randelovic I, Mező D, Schlosser G, Kőhidai L, Tóvári J, Mező G.: Phage Display-Based Homing Peptide-Daunomycin Conjugates for Selective Drug Targeting to PANC-1 Pancreatic Cancer., Pharmaceutics 12: 576, 2020
Al-Majidi M, Szabó D, Dókus L, Steckel A, Mező G, Schlosser G.: Energy‐resolved HCD fragmentation of daunorubicin‐peptide conjugates, J Mass Spectrom 55(10): e4641., 2020
Kis A, Dénes N, Szabó JP, Arató V, Jószai I, Enyedi KN, Lakatos Sz, Garai I, Mező G, Kertész I, Trencsényi Gy.: In vivo assessment of aminopeptidase N (APN/CD13) specificity of different 68Ga-labelled NGR derivatives using PET/MRI imaging., Int J Pharm. 589: 119881, 2020
Borbély A, Pethő L, Szabó I, Al-Majidi M, Steckel A, Nagy T, Kéki S, Kalló G, Csősz É, Mező G, Schlosser G.: Structural characterization of daunomycin-peptide conjugates by various tandem mass spectrometric techniques., Int J Mol Sci 22: 1648, 2021
Dénes N, Kis A, Szabó JP, Jószai I, Hajdu I, Arató V, Enyedi KN, Mező G, Hunyadi J, Trencsényi G, Kertész I.: In vivo preclinical assessment of novel 68Ga-labelled peptides for imaging of tumor associated angiogenesis using positron emission tomography imaging., APPLIED RADIATION AND ISOTOPES 174: 109778, 2021
Kis A, Dénes N, Szabó JP, Arató V, Beke L, Matolay O, Enyedi KN, Méhes G, Mező G, Bai P, Kertész I, Trencsényi G.: In Vivo Molecular Imaging of the Efficacy of Aminopeptidase N (APN/CD13) Receptor Inhibitor Treatment on Experimental Tumors Using 68 Ga-NODAGA-c(NGR) Peptide, Biomed Res Int 2021: Article No.: 6642973, 2021
Dókus Levente E., Lajkó Eszter, Ranđelović Ivan, Mező Diána, Schlosser Gitta, Kőhidai László, Tóvári József, Mező Gábor: Phage Display-Based Homing Peptide-Daunomycin Conjugates for Selective Drug Targeting to PANC-1 Pancreatic Cancer, PHARMACEUTICS 12: (6) p. 576., 2020
Kiss Krisztina, Vass Panna, Farkas Attila, Hirsch Edit, Szabó Edina, Mező Gábor, Nagy Zsombor K., Marosi György: A solid doxycycline HP-beta-CD formulation for reconstitution (i.v. bolus) prepared by scaled-up electrospinning, INTERNATIONAL JOURNAL OF PHARMACEUTICS 586: 119539, 2020
Pethő Lilla, Kasza György, Lajkó Eszter, Láng Orsolya, Kőhidai László, Iván Béla, Mező Gábor: Amphiphilic drug–peptide–polymer conjugates based on poly(ethylene glycol) and hyperbranched polyglycerol for epidermal growth factor receptor targeting: the effect of conjugate aggregation on in vitro activity, SOFT MATTER 16: (24) pp. 5759-5769., 2020
Pethő Lilla, Kasza György, Lajkó Eszter, Láng Orsolya, Kőhidai László, Iván Béla, Mező Gábor: Amphiphilic drug–peptide–polymer conjugates based on poly(ethylene glycol) and hyperbranched polyglycerol for epidermal growth factor receptor targeting: the effect of conjugate aggregation on in vitro activity, SOFT MATTER 16: (24) pp. 5759-5769., 2020
Tripodi A.A.P., Ranđelović I., Biri-Kovács B., Szeder B., Mező G., Tóvári J.: In Vivo Tumor Growth Inhibition and Antiangiogenic Effect of Cyclic NGR Peptide-Daunorubicin Conjugates Developed for Targeted Drug Delivery, PATHOLOGY AND ONCOLOGY RESEARCH 26: (3) pp. 1879-1892., 2020
Ranđelović Ivan, Schuster Sabine, Kapuvári Bence, Fossati Gianluca, Steinkühler Christian, Mező Gábor, Tóvári József: Improved In Vivo Anti-Tumor and Anti-Metastatic Effect of GnRH-III-Daunorubicin Analogs on Colorectal and Breast Carcinoma Bearing Mice, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 20: (19) p. 4763., 2019
Sabine Schuster, Beáta Biri-Kovács, Bálint Szeder, Viktor Farkas, László Buday, Zsuzsanna Szabó, Gábor Halmos, Gábor Mező: Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery, BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY 14: pp. 756-771., 2018
Schuster Sabine, Biri-Kovács Beáta, Szeder Bálint, Buday László, Gardi János, Szabó Zsuzsanna, Halmos Gábor, Mező Gábor: Enhanced In Vitro Antitumor Activity of GnRH-III-Daunorubicin Bioconjugates Influenced by Sequence Modification, PHARMACEUTICS 10: (4) 233, 2018
Vrettos EI, Mező G, Tzakos AG: On the design principles of peptide-drug conjugates for targeted drug delivery to the malignant tumor site, BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY 14: pp. 930-954., 2018
Enyedi KN, Toth S, Szakacs G, Mezo G: NGR-peptide-drug conjugates with dual targeting properties., PLOS ONE 12: (6) e0178632, 2017





 

Events of the project

 
2022-05-02 14:14:05
Résztvevők változása
2022-04-08 14:45:27
Résztvevők változása
2021-02-17 13:39:52
Résztvevők változása
2021-01-29 19:47:56
Kutatóhely váltás
A kutatás helye megváltozott. Korábbi kutatóhely: MTA-ELTE Peptidkémiai Kutatócsoport (Eötvös Loránd Tudományegyetem), Új kutatóhely: Kémiai Intézet (Eötvös Loránd Tudományegyetem).
2020-09-17 15:46:34
Résztvevők változása




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