Krzysztof Z. Felczak, PhD

Research Associate, Center for Drug Design (CDD)

Krzysztof Z. Felczak

Contact Info

felcz001@umn.edu

Office Phone 612-624-2146

Fax 612-626-7610

Office Address:
Nils Hasselmo Hall, Room 4-270
312 Church St SE
Minneapolis, MN 55455

Mailing Address:
MMC 204
312 Church St SE
Minneapolis, MN 55455

Research Associate, Center for Drug Design (CDD)


PhD, Polish Academy of Sciences, Institute of Biochemistry and Biophysics (Chemistry), 1994

University of Warsaw (Chemistry), 1981

Summary

Awards & Recognition

  • Department of Biological Sciences, Polish Academy of Sciences Award “Development of New, Selective Antiviral and Antitumor Analogs of Nucleic Acids Components
  • The Award of the Scientific Secretary of Polish Academy of Sciences for a series of studies on “6- Substituted pyrimidine nucleosides and nucleotides - methods of synthesis, and structure, conformation and biological activity”

Research

Research Summary/Interests

Synthetic Organic Chemistry, Medicinal Chemistry, Drug Design: Anticancer, Antiviral, and Antimicrobial Nucleosides and Nucleotides, Enzyme Inhibitors, NAD-based Therapeutics.

Patents

  • Development of Vaccines Based on Oligosaccharide-Oligonucleotide Conjugates. MacPherson, I.S., Habeshian,S., Krauss, I.J., Hedstrom, L., Felczak, K., Pankiewicz, K.W. Brandeis University, and University of Minnesota 2010.
  • Anti-flavivirus therapeutic. Shi, Pei-Jong., Piug-Basagoiti, F., Pankiewicz, K.W., Felczak, K., Chen, L. PCT/US2009/054468.
  • Novel potent inhibitors of IMP – dehydrogenase. Pankiewicz, K.W., Chen, L., Felczak, K. Center for Drug Design, University of Minnesota. US60/956,730.
  • New analogues of 2’,3’-dideoxy-3’-fluorothymidine with activity against human immunodeficiency viruses HIV-1 and HIV-2, methods of preparation and containing them pharmaceutical compositions. Felczak, K., Miazga, A., Bretner, M., Kulikowski, T. Institute of Biochemistry and Biophysics, Polish Academy of Sciences. P.352532, 2002.
  • New salts of halogenoetylguanines as inhibitors of viruses from family Flaviviridae and antiviral drugs. Borowski, P., Bretner, M., Felczak, K., Kulikowski, T., Schmitz, H. Institute of Biochemistry and Biophysics, Polish Academy of Sciences. P.346996, 2001.

Publications

  • Wang, Y., Wang, W., Xu, L., Zhou, X., Shokrollahi, E., Felczak, K., van der Laan, L.J., Pankiewicz, K.W., Sprengers, D., Raat, N.J., Metselaar, H.J., Peppelenbosch, M.P., Pan, Q. (2016) Crosstalk between Nucleotide Synthesis Pathways with Cellular Immunity in Constraining Hepatitis E Virus Replication. Antimicrob. Agents Chemother. pii: AAC.02700-15. [Epub ahead of print]
  • Pankiewicz, K.W., Petrelli, R., Singh, R., Felczak, K. (2015) Nicotinamide Adenine Dinucleotide Based Therapeutics, Update. Curr. Med. Chem., 22, 3991-4028. 
  • Pankiewicz, K.W.; Felczak, K. (2015) From Ribavirin to NAD Analogues and back to Ribavirin in Search for Anticancer Agents. Heterocyc. Commun. 21, 249 257.
  • Felczak, K., Vince, R., Pankiewicz, K.W. (2014) NAD-based Inhibitors with Anticancer Potential. Bioorg. Med. Chem. Lett. 24, 332-336.
  • Petrelli, R., Vita, P., Torquati, I., Felczak, K., Wilson, D.J., Franchetti, P., Cappellacci, L. (2013) Novel inhibitors of inosine monophosphate dehydrogenase in patent literature of the last decade. Recent Pat. Anticancer Drug Discov. 8, 103-125.
  • Roussel, B., Johnson-Farley, N., Kerrigan, J.E., Scotto, K.W., Banerjee, D., Felczak, K., Pankiewicz, K.W., Gounder, M., Lin, H., Abali, E.E., Bertino, J.R. (2012) A second target of benzamide riboside: dihydrofolate reductase. Cancer Biol Ther. 13, 1290-1298.
  • Wang, J., Sklenak, S., Liu, A., Felczak, K., Wu, Y., Li, Y., Yan, H. (2012) Role of Glutamate 64 in the Activation of the Prodrug 5-Fluorocytosine by Yeast Cytosine Deaminase. Biochemistry 51, 475-486.
  • MacPherson, I.S., Temme, J.S., Habeshian, S., Felczak, K., Pankiewicz, K., Hedstrom, L., Krauss, I.J. (2011) Multivalent Glycocluster Design through Directed Evolution. Angew. Chem. Int. Ed. 50, 11238 –11242.
  • Felczak, K., Pankiewicz K.W. (2011) Synthesis of methylenebis(phosphonate) analogues of 2-, 4-, and 6-pyridones of nicotinamide adenine dinucleotide. Nucleosides, Nucleotides Nucleic Acids 30, 512-523.
  • Petrelli, R., Felczak, K., Cappellacci, L. (2011) NMN/NaMN adenylyltransferase (NMNAT) and NAD kinase (NADK) inhibitors: chemistry and potential therapeutic applications. Curr. Med. Chem. 18, 1973-1992.
  • Felczak, K., Pankiewicz K.W. (2011) Rehab of NAD-dependent enzymes with NAD-based inhibitors; synthesis of methylenebis(phosphonate) analogues of pyridone-3-carboxamide adenine dinucleotides. Coll. Czech Chem. Commun. Symp. Series 12, 204-207.
  • Felczak, K., Pankiewicz, K. W. (2011) Rehab of NAD(P)-Dependent Enzymes with NAD(P)-Based Inhibitors. Curr. Med. Chem. 18, 1891-1908.
  • Felczak, K., Chen, L., Wilson, D., Williams, J., Vince, R., Petrelli, R., Jayaram, H.N., Kusumanchi, P., Kumar, M., Pankiewicz, K.W. (2011) Cofactor-type inhibitors of inosine monophosphate dehydrogenase via modular approach: Targeting the pyrophosphate binding sub-domain. Bioorg. Med. Chem. 19, 1594-1605.
  • Ruda, G.F., Nguyen, C., Ziemkowski, P., Felczak, K., Kasinathan, G., Musso-Buendia, A., Sund, C., Zhou, X.X., Kaiser, M., Ruiz-Pérez, L.M., Brun, R., Kulikowski, T., Johansson, N.G., González-Pacanowska, D., Gilbert, I.H. (2011) Modified 5'-Trityl Nucleosides as Inhibitors of Plasmodium falciparum dUTPase. ChemMedChem 7, 309-320.
  • W?sik, R., ?ebska, M., Felczak, K., Pozna?ski, J., Shugar D. (2010) Relative role of halogen bonds and hydrophobic interactions in inhibition of human protein kinase CK2alpha by tetrabromobenzotriazole and some C(5)-substituted analogues. J. Phys. Chem. B. 114, 10601-10611.
  • Chen, L., Wilson, DJ., Xu, Y., Aldrich, CC., Felczak, K., Sham, YY., Pankiewicz KW. (2010) Triazole-linked inhibitors of inosine monophosphate dehydrogenase from human and Mycobacterium tuberculosis. J. Med. Chem. 53, 4768-4778.
  • Sun, XE., Sharling, L., Muthalagi, M., Mudeppa, DG., Pankiewicz, KW., Felczak, K., Rathod, PK., Mead, J., Striepen, B., Hedstrom, L. (2010) Prodrug activation by Cryptosporidium thymidine kinase. J. Biol. Chem. 285, 15916-15922.
  • Petrelli, R., Sham, YY., Chen, L., Felczak, K., Bennett, E., Wilson, D., Aldrich, C., Yu, JS., Cappellacci, L., Franchetti, P., Grifantini, M., Mazzola, F., Di Stefano, M., Magni, G., Pankiewicz, KW. (2009) Selective inhibition of nicotinamide adenine dinucleotide kinases by dinucleoside disulfide mimics of nicotinamide adenine dinucleotide analogues. Bioorg. Med. Chem. 17, 5656-5664.
  • Zou, G., Puig-Basagoiti, F., Zhang, B., Qing, M., Chen, L., Pankiewicz, KW., Felczak, K., Yuan, Z., Shi, PY. (2009) A single-amino acid substitution in West Nile virus 2K peptide between NS4A and NS4B confers resistance to lycorine, a flavivirus inhibitor. Virology 384, 242-252.
  • Chen, L., Petrelli, R., Felczak, K., Olesiak, M., Bennett, E.M., Magni, G., Pankiewicz, K.W. (2008) Novel Cofactor-Type Inhibitors of NAD-Dependent Enzymes. NAD-Based Therapeutics. Collection Symposium Series 10, 71-79.
  • Chen, L., Petrelli, R., Felczak, K., Gao, G., Bonnac, L., Yu, J.S., Bennett, E.M., Pankiewicz, K.W. (2008) Nicotinamide Adenine Dinucleotide Based Therapeutics. Current Medicinal Chemistry 15, 650-670.
  • Miazga, A., Felczak, K., Siwecka, M.A., Lipniacki, A., Piasek, A., Kulikowski, T. (2007) Synthesis and anti-HIV Properties of Novel 6-Phenylselenenyl-5-propyluracils. Acta Biochim. Polon. 54, 863-868.
  • Ziemkowski, P., Felczak, K., Poznanski, P., Kulikowski, T., Zielinski, Z., Ciesla, J., Rode, W. (2007) Interactions of 2'-fluoro-substituted dUMP analogues with thymidylate synthase. Biochem. Biophys. Res. Commun. 362, 37-43.
  • Chen, L., Gao, G., Felczak, K., Bonnac, L., Patterson, S.E., Wilson, D., Bennett, E., Jayaram, H.N., Hedstrom, L., Pankiewicz, K.W. (2007) Probing Binding Requirements of Type I and Type II Isoforms of Inosine Monophosphate Dehydrogenase with Adenine Modified NAD analogues. J. Med. Chem. 50, 5743-5751.
  • Bonnac, L., Gao, G., Chen, L., Felczak, K., Bennett, E., Xu, H., Kim, T., Liu, N., Oh, H., Tonge, P.J. Pankiewicz, K.W. (2007) Synthesis of 4-phenoxybenzamide adenine dinucleotide as NAD analogue with inhibitory activity against enoyl-ACP reductase (InhA) of Mycobacterium tuberculosis. Bioorganic Medicinal Chemistry Letters 17, 16, 4588-4591.
  • Bonnac, L., Chen, L., Pathak, R., Gao, G., Ming, O., Bennett, E., Felczak, K., Kullberg, M., Patterson, S.E., Mazzola, F., Magni, G., Pankiewicz, K.W. (2007) Probing binding requirements of NAD kinase with modified substrate (NAD) analogues. Bioorganic Medicinal Chemistry Letters 17, 6, 1512-1515.
  • Li, G., Felczak, K., Shi, G., Yan, H. (2006) Mechanism of the conformational transitions in 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase as revealed by NMR spectroscopy. Biochemistry 45, 41, 12573-12581.
  • Jarmula, A., Rypniewski, W. R., Felczak, K., Rode, W. (2005) X-ray crystal and ab initio structures of 3’,5’-di-O-acetyl-N(4)-hydroxy-2’-deoxycytidine and its 5-fluoro analogue: models of the N(4)-OH-dCMP and N(4)-OH-FdCMP molecules interacting with thymidylate synthase. Structural Chemistry 16, 5, 541-549.
  • Miazga, A., Felczak, K., Bretner, M., Siwecka, M.A., Piasek, A., Kulikowski, T. (2003) Thiated analogues of 2’,3’-dideoxy-3’-fluorothymidine and their phosphorylated and phosphonylated derivatives: synthesis, interaction with HIV reverse transcriptase, and in vitro anti-HIV activity. Nucleosides, Nucleotides & Nucleic Acids 22, 973-976.
  • Miazga, A., Golos, B., Zielinski, Z., Ciesla, J., Rode, W., Felczak, K., Wyszynska, K., Kulikowski, T. (2002) Synthesis of 2- or 4-seleno analogues of dUMP, and the corresponding nucleosides. Interactions with mammalian tumour thymidylate synthase of the selenonucleotides and inhibition of tumor cell growth by the selenonucleosides. In: “Chemistry and Biology of Pteridines and Folates.” Eds: S.Milstien, G.Kapatos, R.A. Levine, B.Shane, Kluwer Acad.Publ. Boston p. 467-471.
  • Borowski, P., Niebuhr, A., Mueller, O., Bretner, M., Felczak, K., Kulikowski, T., Schmitz, H. (2001) Purification and characterization of West Nile virus nucleoside triphosphatase (NTPase)/helicase: evidence for dissociation of the NTPase and helicase activities of the enzymes. J. Virol. 75, 3220-3229.
  • Poznanski, J., Felczak, K., Bretner, M., Kulikowski, T,. Remin, M. (2001) 1H NMR conformational study of a variety of ?-anomers of C5-substituted 2’-deoxyuridines: comparison to their antiherpetic ? counterparts. Biochem. Biophys. Res. Commun. 283, 1142-1149.
  • Poznanski, J., Felczak, K., Kulikowski, T., Remin, M. (2000) 1H NMR Conformational study of antiherpetic C5-substituted 2’-deoxyuridines: Insight into the nature of structure-activity relationships. Biochem. Biophys. Res. Commun. 272, 64-74.
  • Rode, W., Dabrowska, M., Zielinski, Z., Golos, B., Wranicz, M., Felczak, K., Kulikowski, T. (2000) Trichinella spiralis and Trichinella pseudospiralis: developmental patterns of enzymes involved in thymidylate biosynthesis and pyrimidine salvage. Parasitology 120, 593-600.
  • Felczak, K., Miazga, A., Poznanski, J., Bretner, M., Kulikowski, T., Dzik, J.M., Golos, B., Zielinski, Z., Ciesla, J., and Rode, W. (2000) 5-Substituted N4-hydroxy-2’-deoxycytidines and their 5’-monophosphates: synthesis, conformation, interaction with tumor thymidylate synthase, and in vitro antitumor activity. J. Med. Chem. 43, 4647-4656.
  • Felczak, K., Bretner, M., Dzik, J.M., Golos, B., Zielinski, Z., Rode, W. and Kulikowski, T. (1998) N4-hydroxy-5-halogeno-2’-deoxycytidines and their 5’-monophosphates as inhibitors of thymidylate synthase and in vitro antileukemic agents. Advances in Experimental Medicine and Biology 431, 617-621.
  • Birnbaum, K.B., Shugar, D., Felczak, K. (1998) 1-(?-D-Ribofuranosyl)-6-propylcytosine. Acta Cryst. C54, 1959-1961.
  • Jarmula, A., Anulewicz, R., Les, A., Cyranski, M.K., Adamowicz, L., Bretner, M., Felczak, K., Kulikowski, T., Krygowski, T.M., Rode, W. (1998) Crystal structures of 5-fluoro-dUrd and its 2 and /or 4-thio analogues: models of substituted dUMP pyrimidine ring interacting with thymidylate synthase. Biochim. Biophys. Acta 1382, 277-286.
  • Felczak, K., Golos, B., Dzik, J.M., Rode, W., Bretner, M., Shugar, D., Kulikowski, T. (1998) Acyclic analogues of 5-fluoro-dUMP and 5-fluoro-2'-deoxyuridine: synthesis and inhibition of thymidylate synthase and tumour cell growth. Acta Biochim. Polon. 45, 75-82.
  • Bretner, M., Felczak, K., Dzik, M., Golos, B., Rode, W., Drabikowska, A., Poznanski, J., Krawiec, K., Piasek, A., Shugar, D., Kulikowski, T.(1997) Thiated pyrimidine deoxynucleoside analogues, potential chemotherapeutic agents, and substrates / inhibitors in various enzyme systems. Nucleosides & Nucleotides, 16, 1295-1299.
  • Dzik, M., Zielinski, Z., Jarmula, A., Michalski, R., Rode, W., Les, A., Bretner, M., Felczak, K., Kulikowski, T. Interaction of thymidylate synthase with 5-hydroxy-dUMP and 5-hydroxymethyl-dUMP, and their 4-thio analogues. in: Chemistry and Biology of Pteridines and Folates, Ed.: Pfleiderer, W., Rokos, H.; Blackwell Sciences, 1997, 415-418.
  • Felczak, K., Drabikowska, A., Vilpo, J.A., Kulikowski, T., Shugar, D. 6-, and 5,6-substituted derivatives of uridine: stereoselective synthesis, interaction with uridine phosphorylase, and in vitro antitumour activity. J. Med. Chem. 1996, 39, 1720-1728.
  • Lapinski, L., Prusinowska, D., Nowak, M.J., Bretner, M., Felczak, K., Maes, G., Adamowicz, L. Infrared spectra of 6-azathiouracils: an experimental matrix isolation and theoretical ab initio SCF/6-311G** study. Spectrochimica Acta Part A, 1996, 52, 645-659.
  • Szyszka, R., Grankowski, N., Felczak, K., Shugar, D. Halogenated benzimidazoles and benzotriazoles as selective inhibitors of protein kinases CKI and CKII from Saccharomyces Cerevisiae and other sources. Biochem. Biophys. Res. Commun. 1995, 208 418-424.
  • Stepinski, J., Bretner, M., Jankowska, M., Felczak, K., Wieczorek, Z., Stolarski, R., Cai, A-L., Rhoads, R.E., Temeriusz, A., Haber, D., Darzynkiewicz, E., Shugar, D. Synthesis and properties of P1,P2-, P1,P3- and P1,P4- dinucleoside di-, tri- and tetraphosphate mRNA 5'-CAP analogues. Nucleosides & Nucleotides, 1995, 14, 717-721.
  • Felczak, K., Bretner, M., Balinska, M., Kulikowski, T. Synthesis and antitumour properties of 2-thio-5-chloropyrimidine nucleosides. Nucleosides & Nucleotides, 1995, 14, 653-656.
  • Felczak, K., Bretner, M., Kulikowski,T., Shugar, D. High - yield regioselective thiation of biologically important pyrimidinones, dihydropyrimidinones and their ribo, 2'-deoxy- ribo and 2',3'-dideoxyribo nucleosides. Nucleosides & Nucleotides, 1993, 12, 245-261.
  • Felczak, K., Kulikowski, T., Vilpo, J.A., Giziewicz, J., Shugar, D. Synthesis and biological properties of 6-substituted 5-fluorouridines. Nucleosides & Nucleotides, 1987, 6, 257-261.