Artur Mucha

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Married, two daughters (Martyna and Paulina).

Hobby: basketball.

E-mail: artur.mucha@pwr.edu.pl

Phone: (48-71) 320 34 46 / 33 54, Fax: (48-71) 320 24 27

Address:

Department of Bioorganic Chemistry

Wrocław University of Technology

Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland


Education

  • 1988 - M.Sc. (Faculty of Chemistry, Wrocław University of Technology)
  • 1995 - Ph.D. (Institute of Organic Chemistry, Biochemistry and Biotechnology, Wrocław University of Technology)
  • 2007 - D.Sc. (Faculty of Chemistry, Wrocław University of Technology)
  • 2016 - Prof. (Faculty of Chemistry, Wrocław University of Technology)


Employment

  • 1988 - Research Assistant / Ph.D. Student
  • 1995 - Assistant Professor
  • 2009 - Associate Professor


Foreign training periods

  • 1993 - Ecole Nationale Superieure de Chimie, Montpellier, France (TEMPUS student, 5 months),
  • 1995 - University of Sheffield, England (TEMPUS visitor, 1 month),
  • 1995-1997 - Departement d'Ingenierie et d'Etudes des Proteines, CEA Saclay, France (post-doctoral stay, 2 years).


Teaching experience

Organic and general chemistry (lectures, seminars and laboratories), multistep organic synthesis, combinatorial chemistry, techniques of reactions on solid support and combinatorial synthesis.

Research interests

The research interests refer to the synthesis and structure of biologically active phosphorus analogues of amino acids and related compounds, with analysis of their enantiomeric composition with the use of chiral selectors. Phosphonamidate and phosphinic pseudopeptides are obtained as inhibitors targeted towards selected proteolytic enzymes, particularly metalloproteases (leucine aminopeptidase, matrixins). The chemical behaviour, stability and activity of such analogues is studied. Both phosphorus and non-phosphorus peptidomimetic inhibitors of cysteine proteases (gingipains, cathepsins) are also developed. The rational design methods are applied to optimise the structure of the active compounds. Chemistry of phosphorus, peptide synthesis on solid phase and in solution as well as combinatorial chemistry are used for the synthesis of psuedopeptides.

Awards

  • Włodzimierz Kołos Prize of Division III (Mathematical, Physical and Chemical Sciences) of Polish Academy of Sciences, 2004
  • Prize of Rector of Wrocław University of Technology, 2011
  • Prize of Rector of Wrocław University of Technology, 2014

Publications

  1. Mucha, A.; Kafarski, P., Peptide and Pseudopeptide Bond Synthesis in Phosphorus Dipeptide Analogs. Methods Mol. Biol. 2020, 2103, 287. View at Publisher
  2. Talma, M.; Mucha, A., P1′ Residue-Oriented Virtual Screening for Potent and Selective Phosphinic (Dehydro) Dipeptide Inhibitors of Metallo-Aminopeptidases Biomolecules 2020, 10, 659. View at Publisher
  3. Janiszewska, K.; Talma, M.; Oszywa, B.; Pawełczak, M.; Kafarski, P.; Mucha, A.,, N-Benzyl Residues as the P1' Substituents in Phosphorus-Containing Extended Transition State Analog Inhibitors of Metalloaminopeptidases Molecules 2020, 25, 4334. View at Publisher
  4. Burda‐Grabowska, M.; Macegoniuk, K.; Flick, R.; Nocek, B. P.; Joachimiak, A.; Yakunin, A. F.; Mucha, A.; Berlicki, Ł., Bisphosphonic acids and related compounds as inhibitors of nucleotide‐ and polyphosphate‐processing enzymes: A PPK1 and PPK2 case study. Chem. Biol. Drug Des. 2019, 93, 1197. View at Publisher
  5. Talma, M.; Maślanka, M.; Mucha, A., Recent developments in the synthesis and applications of phosphinic peptide analogs. Bioorg. Med. Chem. Lett. 2019, 29, 1031. View at Publisher
  6. Maślanka, M.; Mucha, A., Recent Developments in Peptidyl Diaryl Phoshonates as Inhibitors and Activity-Based Probes for Serine Proteases Pharmaceuticals 2019, 12, 86. View at Publisher
  7. Piasta, K.; Dziełak, A.; Mucha, A.; Gumienna-Kontecka, E., Non-symmetrical bis(aminoalkyl)phosphinates: new ligands with enhanced binding of Cu(II) ions. New J. Chem. 2018, 42, 7737. View at Publisher
  8. Ewelina Węglarz-Tomczak, Michał Talma, Mirosław Giurg, Hans V. Westerhoff, Robert Janowski and Artur Mucha, Neutral metalloaminopeptidases APN and MetAP2 as newly discovered anticancer molecular targets of actinomycin D and its simple analogs Oncotarget 2018, 9, 29365. View at Publisher
  9. Ntatsopoulos, V.; Macegoniuk, K.; Mucha, A.; Vassiliou, S.; Berlicki, Ł., Structural exploration of cinnamate-based phosphonic acids as inhibitors of bacterial ureases. Eur. J. Med. Chem. 2018, 159, 307. View at Publisher
  10. Nocek, B. P.; Khusnutdinova, A. N.; Ruszkowski, M.; Flick, R.; Burda, M.; Batyrova, K.; Brown, G.; Mucha, A.; Joachimiak, A.; Berlicki, Ł.; Yakunin, A. F., Structural insights into substrate selectivity and activity of bacterial polyphosphate kinases ACS Catal. 2018, 8, 10746. View at Publisher
  11. Rydzewska, A.; Olender, A.; Mucha, A.; Kafarski, P., Diethyl boronobenzylphosphonates as substrates in Petasis reactions ARKIVOC 2017, 2017, 107. View at Publisher
  12. Talma, M.; Mucha, A., P-C bond formation in reactions of Morita-Baylis-Hillman adducts with phosphorus nucleophiles. Arkivoc 2017, 2017, 324. View at Publisher
  13. Ntatsopoulos, V.; Vassiliou, S.; Macegoniuk, K.; Berlicki, Ł.; Mucha, A., Novel organophosphorus scaffolds of urease inhibitors obtained by substitution of Morita-Baylis-Hillman adducts with phosphorus nucleophiles Eur. J. Med. Chem. 2017, 133, 107. View at Publisher
  14. Macegoniuk, K.; Grela, E.; Biernat, M.; Psurski, M.; Gościniak, G.; Dziełak, A.; Mucha, A.; Wietrzyk, J.; Berlicki, Ł.; Grabowiecka, A., Aminophosphinates against Helicobacter pylori ureolysis—Biochemical and whole-cell inhibition characteristics PLoS One 2017, 1, 182437. View at Publisher
  15. Węglarz-Tomczak, E.; Berlicki, Ł.; Pawełczak, M.; Nocek, B.; Joachimiak, A. Mucha, A., A structural insight into the P1-S1 binding mode of diaminoethylphosphonic and phosphinic acids, selective inhibitors of alanine aminopeptidases. Eur. J. Med. Chem. 2016, 117, 187. View at Publisher
  16. Węglarz-Tomczak, E.; Vassiliou, S.; Mucha, A., Discovery of potent and selective inhibitors of human aminopeptidases ERAP1 and ERAP2 by screening libraries of phosphorus-containing amino acid and dipeptide analogues. Bioorg. Med. Chem. Lett. 2016, 26, 4122. View at Publisher
  17. Węglarz-Tomczak, E.; Staszewska, K.; Talma, M.; Mucha, A., Enantiomeric a,ß-diaminoethylphosphonic acids as potent inhibitors of aminopeptidases — stereoselective synthesis and biological activity. Tetrahedron Lett. 2016, 57, 4812. View at Publisher
  18. Węglarz-Tomczak, E.; Burda-Grabowska, M.; Giurg, M.; Mucha, A., Identification of methionine aminopeptidase 2 as a molecular target of the organoselenium drug ebselen and its derivatives/analogues: Synthesis, inhibitory activity and molecular modeling study. Bioorg. Med. Chem. Lett. 2016, 26, 5254. View at Publisher
  19. Grela, E.; Dziełak, A.; Szydowska, K.; Mucha, A.; Kafarski, P.; Grabowiecka, A.M., Whole-cell Proteus mirabilis urease inhibition by aminophosphinates for the control of struvite formation. J. Med. Microbiol. 2016, 65, 1123. View at Publisher
  20. Macegoniuk, K.; Dziełak, A.; Mucha, A.; Berlicki, Ł., Bis(aminomethyl)phosphinic acid, a highly promising scaffold for the development of bacterial urease inhibitors. ACS Med. Chem. Lett. 2015, 6, 146. View at Publisher
  21. Dziełak, A.; Mucha, A., Catalytic and MW-Assisted Michaelis-Arbuzov Reactions Curr. Green Chem. 2015, 2, 223. View at Publisher
  22. Rudzińska-Szostak, E.; Górecki, Ł. Berlicki, Ł.; Ślepokura, K.; Mucha, A., Zwitterionic Phosphorylated Quinines as Chiral Solvating Agents for NMR Spectroscopy Chirality 2015, 27, 752. View at Publisher
  23. Klimek-Ochab, M.; Mucha, A.; Żymań„czyk-Duda, E, 2-Aminoethylphosphonate Utilization by the Cold-Adapted Geomyces pannorum P11 Strain Curr. Microbiol. 2014, 68, 330. View at Publisher
  24. Górecki, Ł.; Mucha, A.; Kafarski, P., Addition of H-phosphonates to quinine-derived carbonyl compounds. An unexpected C9 phosphonate–phosphate rearrangement and tandem intramolecular piperidine elimination. Beilstein J. Org. Chem. 2014, 10, 883. View at Publisher
  25. Vassiliou, S.; Węglarz-Tomczak, E.; Berlicki, Ł.; Pawełczak, M.; Nocek, B.; Mulligan, R.; Joachimiak, A.; Mucha, A., Structure-guided, single-point modifications in the phosphinic dipeptide structure yield highly potent and selective inhibitors of neutral aminopeptidases. J. Med. Chem. 2014, 57, 8140. View at Publisher
  26. Węglarz-Tomczak, E.; Poręba, M.; Byzia, A.; Berlicki, Ł.; Nocek, B.; Mulligan, R.; Joachimiak, A.; Drąg, M.; Mucha, A., An integrated approach to the ligand binding specificity of Neisseria meningitidis M1 alanine aminopeptidase by fluorogenic substrate profiling, inhibitory studies and molecular modeling. Biochimie 2013, 95, 419. View at Publisher
  27. Górecki, Ł.; Berlicki, Ł.; Mucha, A.; Kafarski, P.; Ślepokura, K.; Rudzińska-Szostak, E., Phosphorylation as a Method of Tuning the Enantiodiscrimination Potency of Quinine – an NMR Study. Chirality 2012, 24, 318. View at Publisher
  28. Mucha, A., Synthesis and Modifications of Phosphinic Dipeptide Analogues Molecules 2012, 17, 13530.
  29. Pícha, J.; Liboska, R.; Buděšínský, M.; Jiráček, J.; Pawełczak, M.; Mucha, A., Unusual activity pattern of leucine aminopeptidase inhibitors based on phosphorus containing derivatives of methionine and norleucine. J. Enz. Inhib. Med. Chem. 2011, 26, 155.
  30. Dziełak, A.; Pawełczak, M.; Mucha, A. , A three-component Mannich-type condensation leading to phosphinic dipeptides – extended transition state analogue inhibitors of aminopeptidases. Tetrahedron Lett. 2011, 52, 3141. View at Publisher
  31. Mucha, A.; Kafarski, P.; Berlicki, Ł., Remarkable potential of the alpha-aminophosphonate/phosphinate structural motif in medicinal chemistry. J. Med. Chem. 2011, 54, 5955. View at Publisher
  32. Skinner-Adams, T. S.; Stack, C. M.; Trenholme, K. R.; Brown, C. L.; Grembecka, J.; Lowther, J.; Mucha, A.; Drag, M.; Kafarski, P.; McGowan, S.; Whisstock, J. C.; Gardiner, D. L.; Dalton, J. P., Plasmodium falciparum neutral aminopeptidases: new targets for anti-malarials. Trends Biochem. Sci. 2010, 35, 53. View at Publisher
  33. McGowan, S.; Oellig, C. A.; Birru, W. A.; Caradoc-Davies, T. T.; Stack, C. M.; Lowther, J.; Skinner-Adams, T.; Mucha, A.; Kafarski, P.; Grembecka, J.; Trenholme, K. R.; Buckle, A. M.; Gardiner, D. L.; Dalton, J. P.; Whisstock, J. C. , Structure of the Plasmodium falciparum M17 aminopeptidase and significance for the design of drugs targeting the neutral exopeptidases. Proc. Natl. Acad. Sci. U. S. A. 2010, 107, 2449. View at Publisher
  34. Mucha, A.; Drą…g, M.; Dalton, J. P.; Kafarski, P., Metallo-aminopeptidase inhibitors. Biochimie 2010, 92, 1509. View at Publisher
  35. McGowan, S.; Porter, C. J.; Lowther. J.; Stack, C. M.; Golding, S. J.; Skinner-Adams, T. S.; Trenholme, K. R.; Teuscher, F.; Donnelly, S. M.; Grembecka, J.; Mucha, A.; Kafarski, P.; Degori, R.; Buckle, A. M.; Gardiner, D. L.; Whisstock, J. C.; Dalton, J. P., Structural basis for the inhibition of the essential Plasmodium falciparum M1 neutral aminopeptidase. Proc. Natl. Acad. Sci. U. S. A. 2009, 106, 2537.
  36. Dąbrowska, E.; Burzyńska, A.; Mucha, A.; Matczak-Jon, E.; Sawka-Dobrowolska, W.; Berlicki, Ł.; Kafarski, P., Insight into the mechanism of three component condensation leading to aminomethylenebisphosphonates. J. Organomet. Chem. 2009, 694, 3806. View at Publisher
  37. Rudzińska, E.; Berlicki, Ł.; Kafarski, P.; Lammerhofer, M.; Mucha, A., Cinchona alkaloids as privileged chiral solvating agents for enantiodiscrimination of N-protected aminoalkanephosphonates - a comparative NMR study. Tetrahedron Asymmetry 2009, 20, 2709. View at Publisher
  38. Mucha, A.; Laemmerhofer, M.; Lindner, W.; Pawełczak, M.; Kafarski, P., Individual stereoisomers of phosphinic dipeptide inhibitor of leucine aminopeptidase. Bioorg. Med. Chem. Lett. 2008, 18, 1550.
  39. Latajka, R.; Krężel, A.; Mucha, A.; Jewgiński, M.; Kafarski, P., Conformational investigations of bis(alpha-aminoalkyl)phosphinic acids and studies of the stability of their complexes with Cu(II). J. Mol. Str. 2008, 877, 64.
  40. Rudzińska, E.; Poliwoda, A.; Berlicki, Ł.; Mucha, A.; Dżygiel, P.; Wieczorek, P.P.; Kafarski, P., Enantiodifferentiation of N-benzyloxycarbonylaminophosphonic and phosphinic acids and their esters using cyclodextrins by means of capillary electrophoresis. J. Chromat. A 2007, 1138, 284. View at Publisher
  41. Stack, C. M.; Lowther, J.; Cunningham, E.; Donnelly, S.; Gardiner, D. L.; Trenholme, K. R.; Skinner-Adams, T. S.; Teuscher, F.; Grembecka, J.; Mucha, A.; Kafarski, P.; Lua, L.; Bell, A.; Dalton, J. P., Characterization of the Plasmodium falciparum M17 leucyl aminopeptidase. A protease involved in amino acid regulation with potential for antimalarial drug development. J. Biol. Chem. 2007, 282, 2069.
  42. Rudzińska, E.; Berlicki, Ł.; Mucha, A.; Kafarski, P., Analysis of pD Dependent Complexation of N-Benzyloxycarbonylaminophosphonic Acids by a-Cyclodextrin. Enantiodifferentation of Phosphonic Acid pKa V alues Chirality 2007, 19, 764. View at Publisher
  43. Rudzińska, E.; Berlicki, Ł.; Mucha, A.; Kafarski, P., Chiral discrimination of ethyl and phenyl N-benzyloxycarbonylaminophosphonates by cyclodextrins. Tetrahedron Asymmetry 2007, 18, 1579. View at Publisher
  44. Berlicki, Ł.; Mucha, A.; Kafarski, P., A mild and convenient oxidation of H-phosphinic acids. Pol. J. Chem. 2007, 81, 1959.
  45. Vassiliou, S.; Xeilari, M.; Yiotakis, A.; Grembecka, J.; Pawelczak, M.; Kafarski, P.; Mucha, A., A synthetic method for diversification of the P1 ' substituent in phosphinic dipeptides as a tool for exploration of the specificity of the S1 ' binding pockets of leucine aminopeptidases. Bioorg. Med. Chem. 2007, 15, 3187.
  46. Teuscher, F.; Lowther, J.; Skinner-Adams, T.S.; Spielmann, T.; Dixon, M.W.A.; Stack, C.M.; Donnelly, S.; Mucha, A.; Kafarski, P.; Vassiliou, S.; Gardiner, D.L.; Dalton, J.P.; Trenholme, K.R., The M18 Aspartyl Aminopeptidase of the Human Malaria Parasite Plasmodium falciparum. J. Biol. Chem. 2007, 282, 30817.
  47. Skinner-Adams, T. S.; Lowther, J.; Teuscher, F.; Stack, C. M.; Grembecka, J.; Mucha, A.; Kafarski, P.; Trenholme, K. R.; Dalton, J. P.; Gardiner, D. L., Identification of Phosphinate Dipeptide Analog Inhibitors Directed against the Plasmodium falciparum M17 Leucine Aminopeptidase as Lead Antimalarial Compounds. J. Med. Chem. 2007, 50, 6024.
  48. Biał‚as, A.; Grembecka, J.; Krowarsch, D.; Otlewski, J.; Potempa, J.; Mucha, A., Exploring the Sn Binding Pockets in Gingipains by Newly Developed Inhibitors: Structure-Based Design, Chemistry and Activity. J. Med. Chem. 2006, 49, 1744.
  49. Mucha, A.; Kunert, A.; Grembecka, J.; Pawelczak, M.; Kafarski, P., A phosphonamidate containing aromatic N-terminal amino group as inhibitor of leucine aminopeptidase-design, synthesis and stability. Eur. J. Med. Chem. 2006, 41, 768.
  50. Preinerstorfer, B.; Lubda, D.; Mucha, A.; Kafarski, P.; Lindner, W.; Lämmerhofer, M., Stereoselective separations of chiral phosphinic acid pseudodipeptides by CEC using silica monoliths modified with an anion-exchange-type chiral selector. Electrophoresis 2006, 27, 4312.
  51. Mucha, A., Fosfonamidowe oraz fosfinopeptydowe inhibitory metaloproteaz. Monografie Wydziału Chemicznego Politechniki Wrocławskiej 2006, 1, 1.
  52. Gał‚ezowska, J.; Sobek, S.; Drag, M.; Mucha, A.; Kafarski, P.; Kozł‚owski, H. , Specific interactions of divalent metal ions with phosphonic analogues of dipeptide inhibitors of proteases. Pol. J. Chem. 2005, 79, 603.
  53. Firczuk, M.; Mucha, A.; Bochtler, M. , Crystal structures of active LytM. J. Mol. Biol. 2005, 354, 579.
  54. Berlicki, Ł.; Rudzińska, E.; Mucha, A.; Kafarski, P., Cyclodextrins as NMR probes in the study of the enantiomeric compositions of N-benzyloxycarbonylamino-phosphonic and phosphinic acids. Tetrahedron-Asymmetry 2004, 15, 1597. View at Publisher
  55. Mucha, A.; Pawelczak, M.; Hurek, J.; Kafarski, P., Synthesis and activity of phosphinic tripeptide inhibitors of cathepsin C. Bioorg. Med. Chem. Lett. 2004, 14, 3113. View at Publisher
  56. Kafarski, P.; Grembecka, J.; Mucha, A.; Pawełczak, M.; Drąg, M.; Berlicki, Ł.; Olechnowicz, D., Projektowanie Potencjalnych Leków i Pestycydów z Wykorzystaniem Wiedzy o Strukturze Przestrzennej Enzymów. Przem. Chem. 2003, 82, 1087.
  57. Mucha, A.; Grembecka, J.; Cierpicki, T.; Kafarski, P., Hydrolysis of the phosphonamidate bond in phosphono dipeptide analogues - The influence of the nature of the N-terminal functional group. Eur. J. Org. Chem. 2003, 4797.
  58. Grembecka, J.; Mucha, A.; Cierpicki, T.; Kafarski, P., The most potent organophosphorus inhibitors of leucine aminopeptidase. Structure-based design, chemistry, and activity. J. Med. Chem. 2003, 46, 2641.
  59. Lammerhofer, M.; Hebenstreit, D.; Gavioli, E.; Lindner, W.; Mucha, A.; Kafarski, P.; Wieczorek, P., High-performance liquid chromatographic enantiomer separation and determination of absolute configurations of phosphinic acid analogues of dipeptides and their alpha-aminophosphinic acid precursors. Tetrahedron-Asymmetry 2003, 14, 2557.
  60. Grembecka, J.; Mucha, A.; Cierpicki, T.; Kafarski, P., Structure-based design and synthesis of dipeptide analogues as new inhibitors of leucine aminopeptidase. Phosphorus, Sulfur 2002, 177, 1739.
  61. Mucha, A.; Grembecka, J.; Białas, A.; Stachowiak, D.; Otlewski, J.; Potempa,J., Design, Synthesis and Activity of Chloromethyl Ketone Inhibitors of Gingipains. Proceeding of the 27th European Peptide Symposium 2002, 988.
  62. Mucha, A.; Kafarski, P., Transesterification of Monophenyl Phosphonamidates - Chemical Modelling of Serine Protease Inhibition. Tetrahedron 2002, 58, 5855.
  63. Mucha, A.; Grembecka, J.; Cierpicki, T.; Kafarski P., The Synthesis of Phosphonamidate and Phosphinic Dipeptide Analogues - Inhibitors of Leucine Aminopeptidase. Biologically Active Peptides. VIIth Conference. Collection Symposium Series 2001, 4, 28.
  64. Vassiliou, S.; Mucha, A.; Cuniasse, P.; Georgiadis, D.; Lucet-Levannier, K.; Beau, F.; Kannan, R.; Murphy, G.; Knauper, V.; Rio, M.-C.; Basset, P.; Yiotakis, A.; Dive, V., Phosphinic Pseudo-Tripeptides as Potent Inhibitors of Matrix Metalloproteinases: A Structure - Activity Study. J. Med. Chem. 1999, 42, 2610.
  65. Holtz, B.; Cuniasse, P.; Boulay, A.; Kannan, R.; Mucha, A.; Beau, F.; Basset, P.; Dive, V., Role of the S1' Subsite Glutamine 215 in Activity and Specificity of Stromelysin-3 by Site-Directed Mutagenesis. Biochemistry 1999, 38, 12174.
  66. Stano, A.; Mucha, A.; Kafarski, P., Reaction of N-(Benzyloxycarbonyl)amino-benzylphosphonous Acid with Triethyl Orthoformate. Synth. Commun. 1999, 29, 4269.
  67. Mucha, A.; Cuniasse, P.; Kannan, R.; Beau, F.; Yiotakis, A.; Basset, P.; Dive, V., Membrane Type-1 Matrix Metalloprotease and Stromelysin-3 Cleave More Efficiently Synthetic Substrates Containing Unusual Amino Acids in Their P1 Positions. J. Biol. Chem. 1998, 273, 2763.
  68. Mucha, A.; Kafarski, P.; Plenat, F.; Cristau, H.-J., Preparation of Benzyl N-Benzyloxycarbonylaminophosphonates and -Aminophospinates - the Scope and Limitations of O-Benzyl-N,N'-dicyclohexylisourea Method. Phosphorus, Sulfur and Silicon 1995, 105, 187.
  69. Mucha, A.; Tyka, R.; Kafarski, P.; Głowiak, T.; Goplańska, A., Preparation, Crystal and Molecular Structure and Evaluation of Plant Growth Regulating Activity of Guanidinoalkanephosphinates and Phosphonates. Heteroatom Chem. 1995, 6, 433.
  70. Mucha, A.; Kafarski, P.; Plenat, F.; Cristau, H.-J., The Preparation of Phosphono Peptides Containing a Phosphonamidate Bond. Tetrahedron 1994, 50, 12743.
  71. Mucha, A.; Tyka, R.; Sawka-Dobrowolska, W.; Głowiak, T., Resolution, Crystal Structure and Absolute Configuration of the Enantiomers of Aminophenylmethane-phosphonous Acid Hydrate. Phosphorus, Sulfur and Silicon 1994, 92, 129.