Máté Erdélyi
Professor vid Institutionen för kemi - BMC; Organisk kemi; Erdelyi grupp
- Telefon:
- 018-471 38 10
- Mobiltelefon:
- 072-999 91 66
- E-post:
- mate.erdelyi@kemi.uu.se
- Besöksadress:
- Husargatan 3
752 37 Uppsala - Postadress:
- Box 576
75123 Uppsala
- ORCID:
- 0000-0003-0359-5970
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Nyckelord
- antibiotic resistance
- halogen bond
- medicinal chemistry
- microwave chemistry
- natural products
- nmr
- organic chemistry
- organic synthesis
- peptide synthesis
- spectroscopy
Biografi
2017- Uppsala University, Uppsala, Sweden
2008- Gothenburg University, Göteborg, Sweden
'Understanding Halogen Bonding in Solution: Investigation of yet unexplored Interactions with application in Medicinal Chemistry' (Swedish Scientific Research Council 2007-4407).
2007-2008 Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
‘Anti-Cancer’ – NMR investigation of tubulin-ligand complexes. Postdoctoral work with Prof. Teresa Carlomagno (Marie-Curie postdoctoral fellowship, FP6 041136).
2005-2006 Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
‘Development of paramagnetic tags for polysaccharides, structural studies using dipolar couplings and paramagnetic shifts’. Postdoctoral work with Prof. Christian Griesinger. (Swedish Scientific Research Council 2004-3073)
2004-2005 University of California, San Diego, USA
‘Investigation of n-s* interactions via solution NMR techniques’. Postdoctoral work with Prof. Charles L. Perrin.
1999-2004 Uppsala University, Uppsala, Sweden
Development of photoswitchable peptidomimetics. Ph.D. work with Prof. A. Gogoll.
1999 Chinoin-Sanofi-Synthelabo Ltd, Budapest, Hungary
NMR-based conformational investigation of berbanes. Project work with Dr. B. Podanyi.
1998 Uppsala University, Uppsala, Sweden
Development of bispidinone and piperazine-based molecular tools for NMR investigation of (p-allyl)palladium complexes. Project work with Prof. A. Gogoll.
1995-1998 Semmelweis University, Budapest, Hungary
Rotamicrospeciation of hydroxycarboxylic acids; investigation of excitatory amino acid analogues. Project work with Prof. B. Noszal.
Research Grants:
2016 Swedish Research Council (2016-05978, proof of concept)
2016 Swedish Research Council (2016-03602, project grant)
2016 Swedish Research Council (2016-05857, development research)
2013 Swedish Research Council (2013-8804, antibiotic resistance)
2013 Sigrud and Elsa Golje's memorial foundation (LA2013-0298)
2012 Swedish Research Council (2012-3819, halogen bonding)
2012 Swedish Research Council (2012-6124, antimalarial natural products)
2012 Swedish Research Council (2012-6074, antitubercular natural products)
2011 Knut Alice Wallenberg Foundation (2011/50)
2010 Carl Tryggers Foundation (CTS 2010:95)
2010 STINT Institutional Grants for Younger Researchers (YR 2010-7045)
2010 European Research Council, Starting Grant (259638)
2010 The Royal Society of Arts and Sciences in Göteborg
2009 Carl Tryggers Foundation (CTS 2009:104)
2009 Åke Wibergs Foundation (8112450333)
2008 Carl Tryggers Foundation (CTS 2008:97)
2007 Swedish Research Council (VR 2007:4407)
Fellowships:
2006 Marie Curie Intra-European fellowship
2006 Humboldt postdoctoral fellowship
2004 Swedish Pharmaceutical Society, fellowship
2004 Vetenskapsrådet, postdoc. fellowship
2003 Swedish Pharmaceutical Society, IF:s Foundation
2002 Swedish Pharm. Society, CD Carlssons Foundation
1998 Fellowship of Pro Renov. Cultura Hungariae Found
Fellowship of the Hungarian Pharmaceutical Society
Fellowship of the Pharmacy for Health Foundation
Fellowship of the Hungarian Academic Stud. Council
1996-9 Fellowship of the Hungarian Republic
Awards:
2004 Pedagogic Prize, Uppsala Pharmaceutical Student Association
1999 Mozsonyi Sándor Award
1998 Schulek Elemér Award
1998 Mozsonyi Sándor Award
Education:
Uppsala University, Uppsala, Sweden
2004 Ph.D. in organic chemistry.
2002 Ph.Lic. in organic chemistry.
Semmelweis University, Budapest, Hungary
1999 Master of Science in Pharmacy
Forskning
Understanding Halogen Bonding in Solution
Halogen bonding is an electron density donation-based weak interaction that has so far mostly been investigated in computational and crystallographic studies.
We examine halogen bonding formed in solution environment employing a novel, exceedingly accurate NMR methodology. Using a combination of spectroscopic and computational techniques the energetics of halogen bonds and the role of electrostatic and non-electrostatic effects in the interaction will be studied. Variation of bond length and symmetry as well as their relevance in inter- and intramolecular interactions are being elucidated.
The gained knowledge will be applied to understand the impact of halogen bonding in biological systems, such as protein-ligand and lipide-ligand interactions as well as used to develop new applications of halogen bonding in organic, analytical and pharmaceutical chemistry.
Exploration of Antimalarial Natural Products from Kenyan Plants
Malaria, caused by the protozoan parasites of the genus Plasmodium, is a major disease in the tropical and subtropical regions of the world. Out of yearly 300 to 500 million clinical episodes, of which 90% occur in tropical sub-Saharan region, 1.5-2.7 million are lethal. Notably, malaria is the leading cause of mortality of children under five years of age and of pregnant women in this area. The emergence of chloroquine-resistant strains of the parasite Plasmodium falciparum and the rising resistance of the vectors (Anopheles spp.) to insecticides in combination with poverty and lack of a well-functioning health care system are the main causes for the increase of malaria morbidity and mortality over the past decade. To date over thousand herbal species are in use in indigenous health systems as means of treating malaria and managing related fever; however, their efficacy and active components have not yet been studied systematically. Although there are several antimalarial drugs on the market, most do not meet the requirement of ≤ 1 USD per treatment and are unaffordable for the majority of Africa. Chloroquine and sulphadoxine-pyrimethamine are the only remedy available for such low price; however, the already widespread and relentlessly increasing resistance against these agents makes them virtually useless. The discovery of Artemisinin from Artemisia annua showed that plants used in traditional medicine may provide new source of lead structures for the development of novel antiplasmodial drugs.
The goal of this ongoing project is identification of novel pharmaceutical lead compounds from the Kenyan flora by evaluation of efficacious traditional remedies by modern techniques. We collaborate with the research group of Prof. Abiy Yenesew at the University of Nairobi, Kenya, and aim to join our forces by integrating cultural practice with modern pharmaceutical approaches to advance new solutions to malaria, the disease of highest mortality in sub-Saharan Africa. Expected outcomes of the project are bioactive natural products rapidly transferable to the treatment of malaria - either through identification of new lead compounds or through development of phytomedicines.
Development of metallo-beta-lactamase inhibitors to control antibiotic resistance
The appearance of superbugs producing metallo-beta-lactamases (MβLs) have resulted in a clinical crisis. In this collaborative project, subclasses of MβLs including NDM-1 are expressed and purified and a a series of beta-lactam antibiotics transition state analogs are synthesized. Their broad-spectrum inhibition activity and structure-activity relationship is evaluated. Special attention will be given to possible synergestic effects when applied in combination with antibiotics for inhibition of antibiotic resistant bacteria. The complexes of MβLs and the transition state analogs are studied by NMR and X-ray crystallography, to provide information useful for the development of clinically applicable broad spectrum inhibitors. The long term goal of this project is to create novel compounds with broad-spectrum inhibitory potency to MβLs and superbugs, and to provide a deeper understanding of molecular processes behind antibiotic action that is expected to support the development of additional antibacterial drugs.
Publikationer
Senaste publikationer
- Exploring the chemical space of orally bioavailable PROTACs (2024)
- Fluorinated captopril analogues inhibit metallo-ll-lactamases and facilitate structure determination of NDM-1 binding pose (2024)
- Molecular chameleons in drug discovery (2024)
- Is Simultaneous Binding to DNA and Gyrase Important for the Antibacterial Activity of Cystobactamids? (2024)
- Benzo[b]naphtho[2,1-d]furans and 2-Phenylnaphthalenes from Streblus usambarensis (2023)
Alla publikationer
Artiklar
- Exploring the chemical space of orally bioavailable PROTACs (2024)
- Fluorinated captopril analogues inhibit metallo-ll-lactamases and facilitate structure determination of NDM-1 binding pose (2024)
- Molecular chameleons in drug discovery (2024)
- Is Simultaneous Binding to DNA and Gyrase Important for the Antibacterial Activity of Cystobactamids? (2024)
- Benzo[b]naphtho[2,1-d]furans and 2-Phenylnaphthalenes from Streblus usambarensis (2023)
- Do non-coordinating polymers function as host materials for solid polymer electrolytes? (2023)
- Crotofolane Diterpenoids and Other Constituents Isolated from Croton kilwae (2023)
- α-Aminophosphonate inhibitors of metallo-β-lactamases NDM-1 and VIM-2 (2023)
- 1-Phospha-Butadienes and 1H-Phospholes via Alkynylation of Acetylenic Phosphaalkenes (2023)
- Macrocyclic Pyrrolizidine Alkaloids and Silphiperfolanol Angelate Esters from Solanecio mannii (2023)
- Going Viral (2023)
- Halogen Bonds of Halogen(I) Ions (2023)
- Ensemble determination by NMR data deconvolution (2023)
- A new β-hydroxydihydrochalcone from Tephrosia uniflora, and the revision of three β-hydroxydihydrochalcones to flavanones (2022)
- Halogen Bond Activation in Gold Catalysis (2022)
- Modified ent-Abietane Diterpenoids from the Leaves of Suregada zanzibariensis (2022)
- Polyoxygenated cyclohexene derivatives and flavonoids from the leaves of Uvaria pandensis (2022)
- Metallo-β-Lactamase Inhibitor Phosphonamidate Monoesters (2022)
- Pushing the Limits of Characterising a Weak Halogen Bond in Solution (2022)
- Linker-Dependent Folding Rationalizes PROTAC Cell Permeability br (2022)
- Synthesis, characterization and computational evaluation of bicyclooctadienes towards molecular solar thermal energy storage (2022)
- Do 2-coordinate iodine(i) and silver(i) complexes form nucleophilic iodonium interactions (NIIs) in solution? (2022)
- Solution Conformations Shed Light on PROTAC Cell Permeability (2021)
- Cell Permeability of Isomeric Macrocycles (2021)
- Employing complementary spectroscopies to study the conformations of an epimeric pair of side-chain stapled peptides in aqueous solution (2021)
- Antiplasmodial and antileishmanial flavonoids from Mundulea sericea (2021)
- Halogen Bonding (2021)
- Solution-State Preorganization of Cyclic β-Hairpin Ligands Determines Binding Mechanism and Affinities for MDM2 (2021)
- Probing Halogen Bonds by Scalar Couplings (2021)
- Biflavanones, Chalconoids, and Flavonoid Analogues from the Stem Bark of Ochna holstii (2021)
- Antibacterial and cytotoxic biflavonoids from the root bark of Ochna kirkii (2021)
- NMReDATA (2021)
- The Influence of Secondary Interactions on the [N−I−N]+ Halogen Bond (2021)
- Modulating photoswitch performance with halogen, coordinative and hydrogen bonding (2021)
- Oxygenated Cyclohexene Derivatives from the Stem and Root Barks of Uvaria pandensis (2021)
- P,N-Chelated Gold(III) Complexes (2021)
- Sulfur Oxidation Increases the Rate of HIRE-Type [1.4]Thiazepinone Ring Expansion and Influences the Conformation of a Medium-Sized Heterocyclic Scaffold (2021)
- Halogen Bonds of Iodonium Ions (2021)
- Halogen Bonding (2021)
- Antibacterial and cytotoxic prenylated dihydrochalcones from Eriosema montanum (2021)
- Antiviral iridoid glycosides from Clerodendrum myricoides (2021)
- Are bis(pyridine)iodine(i) complexes applicable for asymmetric halogenation? (2021)
- Non-uniform sampling for NOESY? (2021)
- Binding of 2-(Triazolylthio)acetamides to Metallo-beta-lactamase CcrA Determined with NMR (2020)
- Prenylated Flavonoids from the Roots of Tephrosia rhodesica (2020)
- Antiplasmodial, Antimicrobial and Cytotoxic Activities of Extracts from Selected Medicinal Plants Growing in Tanzania (2020)
- Solution Conformations Explain the Chameleonic Behaviour of Macrocyclic Drugs (2020)
- An Alternative Approach to the Hydrated Imidazoline Ring Expansion (HIRE) of Diarene-Fused [1.4]Oxazepines (2020)
- O-I-O halogen bond of halonium ions (2020)
- A Meroisoprenoid, Heptenolides, and C-Benzylated Flavonoids from Sphaerocoryne gracilis ssp. gracilis (2020)
- Oxygenated Cyclohexene Derivatives And Other Constituents From The Roots Of Monanthotaxis Trichocarpa (2020)
- Antibacterial activity of 2-amino-3-cyanopyridine derivatives (2020)
- Predicting the permeability of macrocycles from conformational sampling – limitations of molecular flexibility (2020)
- Catalytic Activity of trans-Bis(pyridine)gold Complexes (2020)
- Symmetry of three-center, four-electron bonds (2020)
- Halogen bond of halonium ions (2020)
- Halogen bonds of halonium ions (2020)
- Asymmetric [N–I–N]+ halonium complexes in solution? (2020)
- Halogen bonding in solution (2020)
- Secoiridoids and Iridoids from Morinda asteroscepa (2020)
- Dynamic Chirality in the Mechanism of Action of Allosteric CD36 Modulators of Macrophage-Driven Inflammation (2019)
- A Chemical Biology Approach to Understanding Molecular Recognition of Lipid II by Nisin(1-12) (2019)
- A New Benzopyranyl Cadenane Sesquiterpene and Other Antiplasmodial and Cytotoxic Metabolites from Cleistochlamys kirkii (2019)
- Conformation of the Macrocyclic Drug Lorlatinib in Polar and Nonpolar Environments (2019)
- Mechanism of Au(III)-Mediated Alkoxycyclization of a 1,6-Enyne (2019)
- Halogen Bonding Helicates Encompassing Iodonium Cations (2019)
- Bioactivities of extracts, debromolaurintrerol and fucosterol from Macroalgae species (2018)
- Carbon's Three-Center, Four-Electron Tetrel Bond, Treated Experimentally (2018)
- Halogen Bond Asymmetry in Solution (2018)
- Conformational Sampling of Macrocyclic Drugs in Different Environments (2018)
- NMReDATA, a standard to report the NMR assignment and parameters of organic compounds (2018)
- NMR Determination of the Binding Constant of Ionic Species (2018)
- The Interaction Modes of Haloimidazolium Salts in Solution. (2018)
- Boronic ester-linked macrocyclic lipopeptides as serine protease inhibitors targeting Escherichia coli type I signal peptidase (2018)
- Crystal Structures and Cytotoxicity of ent-Kaurane-Type Diterpenoids from Two Aspilia Species. (2018)
- Three Chalconoids and a Pterocarpene from the Roots of Tephrosia aequilata. (2017)
- Four Prenylflavone Derivatives with Antiplasmodial Activities from the Stem of Tephrosia purpurea subsp. leptostachya. (2017)
- Isoflavones and Rotenoids from the Leaves of Millettia oblata ssp. teitensis. (2017)
- Application of the Halogen Bond in Protein Systems. (2017)
- Introduction to the special issue on halogen bonding. (2017)
- The 15N NMR chemical shift in the characterization of weak halogen bonding in solution. (2017)
- Flavonoids from Erythrina schliebenii. (2017)
- Naphthalene Derivatives from the Roots of Pentas parvifolia and Pentas bussei. (2016)
- Phytoconstituents with Radical Scavenging and Cytotoxic Activities from Diospyros shimbaensis. (2016)
- Flexibility is important for inhibition of the MDM2/p53 protein-protein interaction by cyclic β-hairpins. (2016)
- Pterocarpans and isoflavones from the root bark of Millettia micans and of Millettia dura (2016)
- Solvent effects of nitrogen chemical shifts (2015)
- Counterion influence on the N-I-N halogen bond. (2015)
- Paramagnetic Ligand Tagging To Identify Protein Binding Sites. (2015)
- Halogen bonding in solution. (2015)
- Rotenoids, Flavonoids, and Chalcones from the Root Bark of Millettia usaramensis (2015)
- Halogen bond symmetry: the N–X–N bond (2015)
- Antiplasmodial and cytotoxic activities of the constituents of Turraea robusta and Turraea nilotica. (2015)
- Selenium Accumulating Leafy Vegetables Are a Potential Source of Functional Foods. (2015)
- The impact of interchain hydrogen bonding on β-hairpin stability is readily predicted by molecular dynamics simulation. (2015)
- N-Cinnamoyltetraketide Derivatives from the Leaves of Toussaintia orientalis. (2015)
- Intramolecular Halogen Bonding in Solution: 15N, 13C, and 19F NMR Studies of Temperature and Solvent Effects (2015)
- Cytotoxic quinones from the roots of Aloe dawei. (2014)
- Mapping the sevoflurane-binding sites of calmodulin. (2014)
- A big hello to halogen bonding. (2014)
- The nature of [N–Cl–N]+ and [N–F–N]+ halogen bonds in solution (2014)
- Flemingins G-O, cytotoxic and antioxidant constituents of the leaves of Flemingia grahamiana. (2014)
- Constituents of the roots and leaves of Ekebergia capensis and their potential antiplasmodial and cytotoxic activities. (2014)
- Solvent effects on halogen bond symmetry (2013)
- Insight into β-Hairpin Stability: Interstrand Hydrogen Bonding (2013)
- Anthraquinones of the roots of Pentas micrantha. (2013)
- Solvent effects on 15N NMR coordination shifts. (2013)
- Protonation-triggered Conformational Modulation of an N,N´‑Dialkylbispidine (2013)
- N-Arylation of Protected Azamacrocycles (2013)
- Symmetry of [N-X-N]+ halogen bonds in solution (2012)
- Antiplasmodial quinones from Pentas longiflora and Pentas lanceolata. (2012)
- Busseihydroquinones A-D from the roots of Pentas bussei (2012)
- Dynamics of the glycosidic linkage: conformational space of lactose (2011)
- Paramagnetic lanthanide tagging for NMR conformational analyses of N-linked oligosaccharides. (2011)
- The binding mode of side chain- and C3-modified epothilones to tubulin (2010)
- Conformational preferences of natural and C3-modified epothilones in aqueous solution. (2008)
- One-bond C-C coupling constants in ethers are not primarily determined by N-sigma delocalization. (2005)
- Stereochemistry of beta-deuterium isotope effects on amine basicity. (2005)
- Click chemistry-based bioconjugation of iron oxide nanoparticles
- Macrocyclic pyrrolizidine alkaloids and silphiperfolanol angelate esters from Senecio mannii.
- Exceeding the Limits of Characterising Weak Interactions in Dilute Solutions
- A New NMR Methodology to Study Weak Interactions in Solution
Kapitel
- Halogen-bonded halogen(I) ion complexes (2022)
- The three-center halogen bond (2021)
- Spectroscopy of halogen bonding in solution (2021)
- Solid-phase methods for the synthesis of heterocycles (2006)
Konferenser
- Development of Metallo-β-lactamase Inhibitorsto Control Antibiotic Resistance (2020)
- The three-center halogen bond (2019)
- Solution ensemble analysis of macrocycles (2018)
- Halogen bond promoted peptide folding (2018)
- A cross-platform format to associate NMR-extracted data (NMReDATA) to chemical structures (2018)
- Pentacoordinate carbonium ions in solution (2018)
- The three-centered halogen bond (2018)
- The Halogen Bond of Halonium Ions (2018)
- The three-center-four-electron tetrel bond (2018)
- Asymmetric [N-X-N]+ Halogen Bonds in Solution (2018)
- Development of metallo-β-lactamase inhibitors to controlantibiotic resistance (2018)
- Development of metallo-β-lactamase inhibitors to control antibioticresistance (2018)
- Development of Metallo-β-lactamase Inhibitors to Control Antibiotic Resistance (2018)
- The Solvent Polarity Dependence of Macrocycles’ Conformations (2018)
- Conformational Analysis of Rifampicin in Solution (2018)
- Conformational Analysis of Rifampicin in Solution. (2018)
- Conformational Analysis of Rifampicin in Solution (2018)
- Probing Halogen Bonding via Paramagnetic NMR (2018)
- Probing Halogen Bonding via Paramagnetic Ligand Tagging (2018)
- Paramagnetic lanthanide tags for identifying ligand-protein binding site (2018)
- Halogen and hydrogen bonding - (2017)
- Halogen Bonding: (2017)
- ParLig: (2017)
- 15N NMR chemical shift in the characterisation of halogen bonding in solution (2017)
- The general anaesthetic binding site of Calmodulin disrupts Ryanodine peptide binding (2013)
- A photoswitchable peptide mimetic (2006)
- Development of a stilbene-type photoswitchable β-hairpin mimetic (2005)
- Rapid Microwave-assisted solid-phase peptide synthesis (2003)
- Studies of Photoswitchable β-Hairpin Mimetics (2003)
- Structural Studies of Diastereomeric β-Hairpin Mimetics (2002)