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
