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Development of metallo-β-lactamase inhibitors to controlantibiotic resistance
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry. (Mate Erdelyi)
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry. (Mate Erdelyi)ORCID iD: 0000-0003-3798-3322
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry. (Mate Erdelyi)ORCID iD: 0000-0003-0359-5970
2018 (English)Conference paper, Oral presentation with published abstract (Refereed)
Abstract [en]

According to WHO recent reports indicates one of the biggest problem of XXI century is rapidly growing resistance of bacteria.[1] The most powerful human counter weapon –antibiotics, starts to be an ineffective way in the treatment of bacterial infections. Soonwithout any action we can approach a point when simple infections like pneumonia orSepticemia, will carry a highly probable mortal prognosis.The mostly widely spread mechanism of bacteria resistance is the production of a specificgroup of enzymes β-lactamases, responsible for the degradation or modification of antibiotics,prior to it reaching its target side. At the moment, bacteria need around three months to develop resistance for new type of antibiotics. That is why modern treatment begin toabandon the development of new antibiotics and focuses on inhibitions of β-lactamases andquiet often on metallo-β-lactamases which spectrum is the broadest.The key point of the mechanism of antibiotics hydrolysis by metallo- β -lactamases is creationof tetrahedral intermediate (EI) as a C–N bond-cleaved species. This step indicatesirreversible chemical changes which lead to inactive product.

The aim of this project is focused on existing antibiotics, their transition states - EI andcreation of new bioisosteres, which can have both inhibition and antibiotics properties. Thisstrategy allows for the avoidance of combinatorial therapy and use medicine with widespectrum of action.Further studies of interaction between NDM-1 (New Delhi Metallo-β-Lactamases-1) and synthesized ligands will bring a highly needed and effective way to prevent resistance of bacteria.

Place, publisher, year, edition, pages
2018.
National Category
Chemical Sciences
Research subject
Chemistry with specialization in Organic Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-357815OAI: oai:DiVA.org:uu-357815DiVA, id: diva2:1240493
Conference
16th International School of Biological Magnetic Resonance Course: Frontiers of Biophysics, Erice, Sicily 1-8 August 2018
Available from: 2018-08-21 Created: 2018-08-21 Last updated: 2019-01-03Bibliographically approved

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http://www.puglisilab.org/Erice_2018_Poster.pdf

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Palica, KatarzynaAndersson, HannaErdélyi, Máté

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