The Research Group is concerned with the synthesis and the study of the structure–function relationship of biologically active peptides and their conjugates, mainly in drug targeting and selective diagnostics. Our basic research focuses on peptid conjugates effective against tumours and microbial infections, or suitable for their detection.
The purport of drug targeting is that the entry of the drug into the target cell (tumour cell, infected cell) is facilitated by a component (e.g. peptide) which is able to recognise the target cell with high selectivity. Generally three-component constructs are applied for this purpose: the drug and the targeting molecule are conjugated via a linker moiety. Our main aim is to design peptide conjugates for known or newly identified cell surface structures (e.g. receptors), assisting the selective internalisation of chemotherapeutic agents – those already in clinical use and new ones identified in the Research Group.
An important part of our research is to develop new bifunctional linkers to conjugate the functionalised drug and the targeting peptide; these must enable the liberation of the drug or its active metabolite within the target cell. We aim (aspire, covet) to create a versatile chemical library in which the components can be conjugated to each other in many combinations, thus enlarging the store of conjugates suitable for targeted therapy, which may be a prerequisite for personalised therapy. Apart from the efficiency of the conjugates,their receptor binding, cellular localisation, metabolism and mechanism of actionwill also be studied. These experiments are crucial for choosing the suitable combinations of compounds modifying the effect of each other (e.g. synergistic effect).
Another part of our research is to develop and examine bioconjugates suitable for effective and selective immunotherapy, diagnostics (e.g. in case of microbial infections), and for imaging (e.g. PET, MRI).
For the realisation of the above aims we plan to devise new conjugation strategies, synthetic and analytical methods. Our research is closely associated to EU H2020 and to priority topics of WHO, and international collaborations.
Position and perspectives of peptide chemistry:
Peptide chemistry as an individual discipline has a ca. 70-80 year-old past. The aim of peptide synthesis used to be mainly the better understanding of biochemical procedures via modelling of proteins. The pharmacological application of peptides was less important at the time. As a rare exception, our Research Group has already participated in 1967 in the then world sensation synthesis of human ACTH (Kálmán Medzihradszky and his co-workers). Instead of the earlier heuristic view, nowadays a new, more conscious, designed approach is in the front line, designing drugs against different diseases based on the knowledge of the molecular details of pathobiochemical processes. In the place of the earlier methodsbased on "classic" organic chemistry applying Lipinski’s rule of five in drug research, in the last few decades the deliberate, target specific, selective approach is chosen. Development of peptide based drugs is booming, because the peptides are more specific and less toxic then the small molecular weight organic drugs, as they accumulate less in the tissues. Apart from these, the high biological and chemical versatility of the peptides may make it possible to target several diseases. The change of paradigm in the drug discovery has placed the peptide chemistry in lime light again. The former, basic research like peptide chemical projects have grown towards the conscious drug design, and even towards personalised therapies. This process is characterised by the fact that at present there are more than 70, peptide or peptide based registered drugs available, more than 140 in clinical, more than 500 in preclinical trial phase.
The MTA-ELTE Research Group of Peptide Chemistry, founded in 1961 by Győző (Victor) Bruckner as the first Hungarian workshop, has been continuously adding to the 80-year success story of the peptide chemical researches. In human resources (knowledge, know-how, personal and institutional network), in its unique instrumentation and in establishing knowledge transfer our Research Group belongs to the world-wide known, recognised schools of peptide chemistry with a long tradition. As the impact of peptide chemistry is expected to grow in the field of drug discovery, the existence and development of such a complex knowledge base as the Research Group has a high importance in science, economy and education.
Conferences/Workshops organised by the Research Group:
1990: Workshop on Bioconjugates, 20th FEBS Meeting, Budapest
1992: Prediction and Recognition of Antigenic Determinants, a Satellite Meeting of the 8th International Congress of Immunology, Budapest
1995: Synthetic Polymers in Drug Delivery Research, 3rd Annual Meeting of the SPIDER Network (EU PECO Initiative), Budapest
1998: 25th European Peptide Symposium, Budapest
2000: Peptide Based Synthetic Antigens Against Infectious Diseases, 1st Annual Meeting of the Working Group (COST), Budapest
2003: Workshop on "Cellular Transport Strategies for Targeting Epitopes, Drugs and Reporter Molecules" (QLAM-CT-2002-30585), EU FP5 Quality of Life
2005: Workshop on Bioconjugates, 30th FEBS Meeting, Budapest
2014: Chemical Approaches to Targeting Drug Resistance in Cancer Stem Cells, CMST COST Action CM1106 Workshop, Budapest
2016: Workshop on "Direct Reaction Monitoring and Compound Identification by Mass Spectrometry", ELTE, Budapest
2016: Mass Spectrometry Summer School (supported by MTA MedInProt), ELTE, Budapest
2017: X-ray Crystallography and Protein Identification by Mass Spectrometry Summer School (supported by MTA MedInProt), ELTE, Budapest
Mission driven research:
Research at the Research Group of Peptide Chemistry (RGPC) has been closely related to priorities of EU, NATO and WHO, international collaborations supported by Hungarian (OTKA, OMFB, Ministry of Education, Ministry of Health, Hungarian Academy of Sciences), and international agencies (WHO, EACR, NATO, EU-COST). RGPC is involved in contract research for Hungarian (Reanal, Biosignal, G. Richter) and foreign companies (Pliva, Croatia; Veterinary Agency, UK; Unilever, UK).