Building up modern infrastructure to characterise new synthetic and natural anti-tumour and antimicrobial agents and their target delivery conjugates (Q3958270): Difference between revisions
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A) Presentation of the tasks to be implemented: The aim of the project is to acquire and operate a set of instruments that are suitable for identifying/characterising new natural (plant, fungal and bacterial) organic compounds and organic compounds produced by chemical synthesis, their conjugates (directive derivatives, colloidal nanoparticles) and their metabolites, as well as for researching protein-level changes (proteomics) in cells due to the influence of compounds. In the treatment of both tumour and re-infectious diseases of microbial origin, a major breakthrough can be made by so-called directed therapy, which increases the selectivity of active substances and reduces their side effects. The common feature of this new direction of pharmaceutical research is the creation of compounds that are able to target the active substance into the affected tumour or infected cell. The infrastructure to be developed aims at the isolation, identification and characterisation of new naturally produced biologically active compounds (conjugates with peptide and/or nanosystems) produced by organic chemical synthesis, in line with the highest international standards. The vast majority of biologically active substances currently used in medicine are secondary metabolites of plants, fungi and procaryote microorganisms or are related semi-synthetic synthetic compounds. One of the main objectives of our research is to identify and characterise new active substances and metabolites of plant, fungal or micro-organism origin. With this infrastructural development, we aim to broaden the possibility of discovering additional medicinal and toxic plant active substances and the characterisation profile of the compounds. In the course of research, we define not only an active substance of an organism, but also an increasingly fundamental “metabolite fingerprint” in international practice. It is important to note that, according to some hypotheses, most of the previously unknown active substances can be effectively identified and characterised by this strategy. For similar reasons, metabolic characterisation of metabolic products of microbes living in extreme conditions is promising (professional responsible: Institute of Biology, Department of Plant Organology, Department of Microbiology). The majority of bioconjugates suitable for targeted therapy consist of three components; active substance, controlling molecule and interconnecting unit. In our research we attempt to create compound stores in which the active substance (natural or synthesised) and controlling peptide components can be linked together in a wide range of combinations with the developed bifunction linkers, increasing the range of conjugates suitable for targeted therapy, which can also be a prerequisite for personalised healing. In addition to the identification and characterisation of the components produced and the conjugates produced from them, their stability, metabolism and cell-induced protein-level changes in biological systems are also essential for the measurement of their highly permeable, highly disruptive analytical platform (professional operator: Institute of chemistry, MTA-ELTE Peptidchemical Research Group). The above two research areas jointly rely on the newly procured “cutting edge” UHPLC-MS/MS device, which is not only suitable for simple routine analyses, but also has significant research potential. Qualitative and quantitative analysis of the components of the samples may be carried out using a system (HPLC-MS/MS) associated with liquid chromatography (HPLC) designed for procurement, allowing high-accuracy mass determination, with quadrupol and orbitrap mass detection. The quantity of components to be tested may vary by order of magnitude. The system is suitable for performing ultra-efficient liquid chromatography (UHPLC) tests, significantly shortening the measurement time, thereby increasing the number of samples that can be processed and reducing solvent use. The identification and quantification of separated substances is provided by a diode array detector (190-800 nm), high-resolution mass specrometry detection by the hybrid quadrupol-orbitrap mass spectrometer. Operating over a wide mass range (m/z 50-2000) with high precision (less than 5 ppm) mass spectrometers also allow for structural identification and pollution profile identification by providing a unique sensitivity (attogram). Ms/MS recording is provided by a high-energy HCD impact cell, which allows reproducible spectrum recording and more secure component identification for library search. Interchangeable ion sources (API ion source housing with heated electrospray ionisation — H-ESI II and APCI ionisation sources with dual distillation system) allow the examination of molecules of a wide variety of structures. The main characteristics listed make the instrument suitable for rapid “high throughput” analysis of a large number of samples. A (English) | |||||||||||||||
| Property / summary: A) Presentation of the tasks to be implemented: The aim of the project is to acquire and operate a set of instruments that are suitable for identifying/characterising new natural (plant, fungal and bacterial) organic compounds and organic compounds produced by chemical synthesis, their conjugates (directive derivatives, colloidal nanoparticles) and their metabolites, as well as for researching protein-level changes (proteomics) in cells due to the influence of compounds. In the treatment of both tumour and re-infectious diseases of microbial origin, a major breakthrough can be made by so-called directed therapy, which increases the selectivity of active substances and reduces their side effects. The common feature of this new direction of pharmaceutical research is the creation of compounds that are able to target the active substance into the affected tumour or infected cell. The infrastructure to be developed aims at the isolation, identification and characterisation of new naturally produced biologically active compounds (conjugates with peptide and/or nanosystems) produced by organic chemical synthesis, in line with the highest international standards. The vast majority of biologically active substances currently used in medicine are secondary metabolites of plants, fungi and procaryote microorganisms or are related semi-synthetic synthetic compounds. One of the main objectives of our research is to identify and characterise new active substances and metabolites of plant, fungal or micro-organism origin. With this infrastructural development, we aim to broaden the possibility of discovering additional medicinal and toxic plant active substances and the characterisation profile of the compounds. In the course of research, we define not only an active substance of an organism, but also an increasingly fundamental “metabolite fingerprint” in international practice. It is important to note that, according to some hypotheses, most of the previously unknown active substances can be effectively identified and characterised by this strategy. For similar reasons, metabolic characterisation of metabolic products of microbes living in extreme conditions is promising (professional responsible: Institute of Biology, Department of Plant Organology, Department of Microbiology). The majority of bioconjugates suitable for targeted therapy consist of three components; active substance, controlling molecule and interconnecting unit. In our research we attempt to create compound stores in which the active substance (natural or synthesised) and controlling peptide components can be linked together in a wide range of combinations with the developed bifunction linkers, increasing the range of conjugates suitable for targeted therapy, which can also be a prerequisite for personalised healing. In addition to the identification and characterisation of the components produced and the conjugates produced from them, their stability, metabolism and cell-induced protein-level changes in biological systems are also essential for the measurement of their highly permeable, highly disruptive analytical platform (professional operator: Institute of chemistry, MTA-ELTE Peptidchemical Research Group). The above two research areas jointly rely on the newly procured “cutting edge” UHPLC-MS/MS device, which is not only suitable for simple routine analyses, but also has significant research potential. Qualitative and quantitative analysis of the components of the samples may be carried out using a system (HPLC-MS/MS) associated with liquid chromatography (HPLC) designed for procurement, allowing high-accuracy mass determination, with quadrupol and orbitrap mass detection. The quantity of components to be tested may vary by order of magnitude. The system is suitable for performing ultra-efficient liquid chromatography (UHPLC) tests, significantly shortening the measurement time, thereby increasing the number of samples that can be processed and reducing solvent use. The identification and quantification of separated substances is provided by a diode array detector (190-800 nm), high-resolution mass specrometry detection by the hybrid quadrupol-orbitrap mass spectrometer. Operating over a wide mass range (m/z 50-2000) with high precision (less than 5 ppm) mass spectrometers also allow for structural identification and pollution profile identification by providing a unique sensitivity (attogram). Ms/MS recording is provided by a high-energy HCD impact cell, which allows reproducible spectrum recording and more secure component identification for library search. Interchangeable ion sources (API ion source housing with heated electrospray ionisation — H-ESI II and APCI ionisation sources with dual distillation system) allow the examination of molecules of a wide variety of structures. The main characteristics listed make the instrument suitable for rapid “high throughput” analysis of a large number of samples. A (English) / rank | |||||||||||||||
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| Property / summary: A) Presentation of the tasks to be implemented: The aim of the project is to acquire and operate a set of instruments that are suitable for identifying/characterising new natural (plant, fungal and bacterial) organic compounds and organic compounds produced by chemical synthesis, their conjugates (directive derivatives, colloidal nanoparticles) and their metabolites, as well as for researching protein-level changes (proteomics) in cells due to the influence of compounds. In the treatment of both tumour and re-infectious diseases of microbial origin, a major breakthrough can be made by so-called directed therapy, which increases the selectivity of active substances and reduces their side effects. The common feature of this new direction of pharmaceutical research is the creation of compounds that are able to target the active substance into the affected tumour or infected cell. The infrastructure to be developed aims at the isolation, identification and characterisation of new naturally produced biologically active compounds (conjugates with peptide and/or nanosystems) produced by organic chemical synthesis, in line with the highest international standards. The vast majority of biologically active substances currently used in medicine are secondary metabolites of plants, fungi and procaryote microorganisms or are related semi-synthetic synthetic compounds. One of the main objectives of our research is to identify and characterise new active substances and metabolites of plant, fungal or micro-organism origin. With this infrastructural development, we aim to broaden the possibility of discovering additional medicinal and toxic plant active substances and the characterisation profile of the compounds. In the course of research, we define not only an active substance of an organism, but also an increasingly fundamental “metabolite fingerprint” in international practice. It is important to note that, according to some hypotheses, most of the previously unknown active substances can be effectively identified and characterised by this strategy. For similar reasons, metabolic characterisation of metabolic products of microbes living in extreme conditions is promising (professional responsible: Institute of Biology, Department of Plant Organology, Department of Microbiology). The majority of bioconjugates suitable for targeted therapy consist of three components; active substance, controlling molecule and interconnecting unit. In our research we attempt to create compound stores in which the active substance (natural or synthesised) and controlling peptide components can be linked together in a wide range of combinations with the developed bifunction linkers, increasing the range of conjugates suitable for targeted therapy, which can also be a prerequisite for personalised healing. In addition to the identification and characterisation of the components produced and the conjugates produced from them, their stability, metabolism and cell-induced protein-level changes in biological systems are also essential for the measurement of their highly permeable, highly disruptive analytical platform (professional operator: Institute of chemistry, MTA-ELTE Peptidchemical Research Group). The above two research areas jointly rely on the newly procured “cutting edge” UHPLC-MS/MS device, which is not only suitable for simple routine analyses, but also has significant research potential. Qualitative and quantitative analysis of the components of the samples may be carried out using a system (HPLC-MS/MS) associated with liquid chromatography (HPLC) designed for procurement, allowing high-accuracy mass determination, with quadrupol and orbitrap mass detection. The quantity of components to be tested may vary by order of magnitude. The system is suitable for performing ultra-efficient liquid chromatography (UHPLC) tests, significantly shortening the measurement time, thereby increasing the number of samples that can be processed and reducing solvent use. The identification and quantification of separated substances is provided by a diode array detector (190-800 nm), high-resolution mass specrometry detection by the hybrid quadrupol-orbitrap mass spectrometer. Operating over a wide mass range (m/z 50-2000) with high precision (less than 5 ppm) mass spectrometers also allow for structural identification and pollution profile identification by providing a unique sensitivity (attogram). Ms/MS recording is provided by a high-energy HCD impact cell, which allows reproducible spectrum recording and more secure component identification for library search. Interchangeable ion sources (API ion source housing with heated electrospray ionisation — H-ESI II and APCI ionisation sources with dual distillation system) allow the examination of molecules of a wide variety of structures. The main characteristics listed make the instrument suitable for rapid “high throughput” analysis of a large number of samples. A (English) / qualifier | |||||||||||||||
point in time: 9 February 2022
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Revision as of 18:46, 9 February 2022
Project Q3958270 in Hungary
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | Building up modern infrastructure to characterise new synthetic and natural anti-tumour and antimicrobial agents and their target delivery conjugates |
Project Q3958270 in Hungary |
Statements
203,652,385 forint
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742,279.164 Euro
0.0027336256 Euro
15 December 2021
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271,536,513.333 forint
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74.999999 percent
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1 July 2017
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28 September 2020
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EÖTVÖS LORÁND TUDOMÁNYEGYETEM
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47°29'30.62"N, 18°58'44.15"E
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A) A megvalósítani kívánt feladatok bemutatása: A projekt célja olyan műszeregyüttes beszerzése és működtetése, amely egyaránt alkalmas új természetes (növény, gomba és bakteriális) eredetű izolált, illetve kémiai szintézissel előállított szerves vegyületek, konjugátumaik (célbajuttató származékok, kolloidális nanorészecskék) valamint metabolitjaik azonosítására/jellemzésére, továbbá a vegyületek hatására a sejtekben bekövetkező fehérje szintű változások (proteomika) kutatására. Mind a tumoros, mind az újra növekvő számú mikrobiális eredetű fertőző betegségek gyógyításában jelentős áttörést hozhat az ún. irányított terápia, amely növeli a hatóanyagok szelektivitását és csökkenti azok mellékhatását. Ezen új gyógyszerkutatási irány közös jellemzője olyan vegyületek létrehozása, amelyek képesek a hatóanyagot célzottan az érintett tumor, illetve fertőzött sejtbe juttatni. A kialakítandó infrastruktúra az új természetes eredetű, biológiailag aktív vegyületek izolálását, azonosítását és a szerves kémiai szintézissel előállított új vegyületek (peptid- és/vagy nanorendszerekkel kialakított konjugátumok) jellemezését kívánja – a legmagasabb nemzetközi elvárásoknak megfelelően – szolgálni. A gyógyászatban jelenleg használt biológiailag aktív hatóanyagok döntő többsége növények, gombák és prokarióta mikroorganizmusok másodlagos anyagcsereterméke, vagy ezekhez köthető félszintetikus, szintetikus vegyület. Kutatásaink egyik fő célja új, eddig ismeretlen növényi, gomba- vagy mikroorganizmus eredetű hatóanyagok és metabolitok azonosítása és jellemzése. Ezen infrastrukturális fejlesztéssel szélesíteni kívánjuk a további gyógy- és mérgező növény hatóanyagok felfedezésének lehetőségét és a vegyületek jellemzési profilját. A kutatások során nem csupán egy adott organizmus eredetű hatóanyagot, hanem a nemzetközi gyakorlatban is egyre alapvetőbb „metabolit-ujjlenyomatot” is meghatározzuk. Fontosnak tartjuk megjegyezni, hogy egyes hipotézisek szerint a legtöbb eddig ismeretlen hatóanyag ezzel a stratégiával azonosítható és jellemezhető eredményesen. Hasonló okokból ígéretes a szélsőséges körülmények között élő mikrobák anyagcsere termékeinek metabolikus jellemzése is (szakmai felelős: Biológiai Intézet, Növényszervezettani Tanszék, Mikrobiológiai Tanszék). A célzott terápiára alkalmas biokonjugátumok többsége három komponensből áll; hatóanyag, irányító molekula és az ezeket összekapcsoló egység. Kutatásunkban arra teszünk kísérletet, hogy olyan vegyülettárakat hozzunk létre, amelyekben a hatóanyag (természetes eredetű vagy szintetizált) és irányító peptid komponensek a kifejlesztett bifunkciós linkerek segítségével sokféle kombinációban kapcsolhatók egymáshoz, növelve a célzott terápiára alkalmas konjugátumok választékát, ami a személyre szabott gyógyítás alapfeltétele is lehet. Az előállított komponensek és a belőlük készített konjugátumok azonosítása és jellemzése mellett a biológiai rendszerekben mért stabilitásuk, metabolizmusuk és a sejtekben általuk kiváltott fehérjeszintű változások méréséhez is elengedhetetlen az alábbiakban bemutatott nagyáteresztő képességű, nagy felbontóképességű elemző platform (szakmai felelős: Kémiai Intézet, MTA-ELTE Peptidkémiai Kutatócsoport). A fenti két kutatási terület közösen támaszkodik az újonnan beszerzendő „cutting edge” UHPLC-MS/MS készülékre, amely nem csak egyszerű rutin analízisekre alkalmas, hanem jelentős kutatási potenciált is hordoz. A minták komponenseinek minőségi és mennyiségi analízise a beszerzésre tervezett folyadékkromatográfiával (HPLC) kapcsolt, nagypontosságú tömegmeghatározást lehetővé tevő, kvadrupol és orbitrap tömegdetektálással rendelkező rendszer (HPLC-MS/MS) alkalmazásával valósítható meg. A vizsgálandó összetevők mennyisége akár több nagyságrendnyi eltérést is mutathat. A rendszer alkalmas ultrahatékony folyadékkromatográfiás (UHPLC) vizsgálatok kivitelezésére, jelentősen lerövidítve a mérési időt, ezzel növelve a feldolgozható minták számát és csökkentve az oldószer felhasználást. Az egymástól elválasztott anyagok azonosítását és mennyiségi meghatározását diódasoros detektor (190-800 nm), a nagyfelbontású tömegspekrometriás detektálást a hibrid kvadrupol-orbitrap tömegspektrométer biztosítja. A széles tömegtartományban (m/z 50-2000), nagy pontossággal (5 ppm alatt) működő tömegspektrométer szerkezetazonosítást és szennyezés profil azonosítást is lehetővé tesz egyedülálló érzékenység (attogram) biztosításával. MS/MS felvételre nagyenergiájú ütköztetést biztosító HCD ütközési cella ad lehetőséget, amellyel könyvtárkeresésre alkalmas, reprodukálható spektrumfelvétel készítés és még biztosabb komponensazonosítás valósítható meg. A cserélhető ionforrások (API ionforrás ház fűtött, kettős deszolvatációs rendszerrel rendelkező electrospray ionizációs - H-ESI II - és APCI ionforrásokkal) a legkülönbözőbb szerkezetű molekulák vizsgálatát teszik lehetővé. A felsorolt főbb jellemzők alkalmassá teszik a műszert nagyszámú minta gyors, „high throughput” elemzésére. A k (Hungarian)
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A) Presentation of the tasks to be implemented: The aim of the project is to acquire and operate a set of instruments that are suitable for identifying/characterising new natural (plant, fungal and bacterial) organic compounds and organic compounds produced by chemical synthesis, their conjugates (directive derivatives, colloidal nanoparticles) and their metabolites, as well as for researching protein-level changes (proteomics) in cells due to the influence of compounds. In the treatment of both tumour and re-infectious diseases of microbial origin, a major breakthrough can be made by so-called directed therapy, which increases the selectivity of active substances and reduces their side effects. The common feature of this new direction of pharmaceutical research is the creation of compounds that are able to target the active substance into the affected tumour or infected cell. The infrastructure to be developed aims at the isolation, identification and characterisation of new naturally produced biologically active compounds (conjugates with peptide and/or nanosystems) produced by organic chemical synthesis, in line with the highest international standards. The vast majority of biologically active substances currently used in medicine are secondary metabolites of plants, fungi and procaryote microorganisms or are related semi-synthetic synthetic compounds. One of the main objectives of our research is to identify and characterise new active substances and metabolites of plant, fungal or micro-organism origin. With this infrastructural development, we aim to broaden the possibility of discovering additional medicinal and toxic plant active substances and the characterisation profile of the compounds. In the course of research, we define not only an active substance of an organism, but also an increasingly fundamental “metabolite fingerprint” in international practice. It is important to note that, according to some hypotheses, most of the previously unknown active substances can be effectively identified and characterised by this strategy. For similar reasons, metabolic characterisation of metabolic products of microbes living in extreme conditions is promising (professional responsible: Institute of Biology, Department of Plant Organology, Department of Microbiology). The majority of bioconjugates suitable for targeted therapy consist of three components; active substance, controlling molecule and interconnecting unit. In our research we attempt to create compound stores in which the active substance (natural or synthesised) and controlling peptide components can be linked together in a wide range of combinations with the developed bifunction linkers, increasing the range of conjugates suitable for targeted therapy, which can also be a prerequisite for personalised healing. In addition to the identification and characterisation of the components produced and the conjugates produced from them, their stability, metabolism and cell-induced protein-level changes in biological systems are also essential for the measurement of their highly permeable, highly disruptive analytical platform (professional operator: Institute of chemistry, MTA-ELTE Peptidchemical Research Group). The above two research areas jointly rely on the newly procured “cutting edge” UHPLC-MS/MS device, which is not only suitable for simple routine analyses, but also has significant research potential. Qualitative and quantitative analysis of the components of the samples may be carried out using a system (HPLC-MS/MS) associated with liquid chromatography (HPLC) designed for procurement, allowing high-accuracy mass determination, with quadrupol and orbitrap mass detection. The quantity of components to be tested may vary by order of magnitude. The system is suitable for performing ultra-efficient liquid chromatography (UHPLC) tests, significantly shortening the measurement time, thereby increasing the number of samples that can be processed and reducing solvent use. The identification and quantification of separated substances is provided by a diode array detector (190-800 nm), high-resolution mass specrometry detection by the hybrid quadrupol-orbitrap mass spectrometer. Operating over a wide mass range (m/z 50-2000) with high precision (less than 5 ppm) mass spectrometers also allow for structural identification and pollution profile identification by providing a unique sensitivity (attogram). Ms/MS recording is provided by a high-energy HCD impact cell, which allows reproducible spectrum recording and more secure component identification for library search. Interchangeable ion sources (API ion source housing with heated electrospray ionisation — H-ESI II and APCI ionisation sources with dual distillation system) allow the examination of molecules of a wide variety of structures. The main characteristics listed make the instrument suitable for rapid “high throughput” analysis of a large number of samples. A (English)
9 February 2022
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Budapest, Budapest
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Identifiers
VEKOP-2.3.3-15-2017-00020
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