Dr. Frank Schweizer
 

Associate Professor Department of Chemistry and Assistant Professor Medical Microbiology, University of Manitoba

Degrees: Ph.D. University of Alberta (1999), Dipl. Chem. Albert-Ludwigs University Freiburg , Germany (1993)

Mailing Address: Department of Chemistry, 460 Parker Building, 144 Dysart Rd. Winnipeg , Manitoba R3T 2N2

Tel: (204) 474-7012
 
Email: Frank.Schweizer@umanitoba.ca
Website: home.cc.umanitoba.ca/~schweize

 

Research Interests: 
Development of novel antibiotics, antimicrobial peptidomimetics, aminoglycosides, glycobiology of infection, drug discovery and preclinical evaluation of antibacterial lead structures, protein folding, structural glycobiology, chemical biology of aging

Selected Recent Publications: (2012-2007)

For a list of Dr. Schweizer's PubMed articles, please click here

 

  1.  Zhanel, G.G., Schweizer, F., Karlowsky, J.A. Oritavancin: Mechanism of action. Clin. Infect. Diseases (in press 2012).
  2. Findlay, B., Zhanel, G.G.; Schweizer, F. Investigating the antimicrobial peptide “window of activity” using cationic lipopeptides with hydrocarbon and fluorinated tails. Int. J. Antimicrob. Agents (in press 2012)
  3. Zhanel, G.G., Lawson, C.D., Zelenitsky, A., Findlay, B., Schweizer, F., Adam, H., Walkty, A., Rubinstein, E., Gin, A.S., Hoban, D.J., Lynch, J.P., Karlowsky, J.A.. Comparison of the next generation aminoglycoside plazomicin (ACHN-490) to gentamicin, tobramycin, and amikacin. Exp. Rev. Antiinfect. Ther. (in press 2012).
  4. Findlay, B., Zhanel, G.G., Schweizer, F. Neomycin-phenolic conjugates: Polycationic amphiphiles with broad-spectrum antibacterial activity, low haemolytic activity and weak serum protein binding. Bioorg. Med. Chem. Lett. 22, 1499-1503 (2012).
  5. Naziga, E.B., Schweizer, F., Wetmore, S.D. Conformational study of the hydroxyproline-O-glycosidic linkage: Sugar-peptide orientation and prolyl amide isomerization in (a,b)-galactosylated 4(R/S)-hydroxyproline. J. Phys. Chem. B. 116, 860-871 (2012).
  6. Koizumi, A., Yamano, K., Schweizer, F., Takeda, T., Kiuchi, F., Hada, N. Synthesis of the carbohydrate moiety of the parasite Echinococcus multilocularis and their antigenicity against human sera. Eur. J. Med. Chem. 46, 1768-1778 (2011). 
  7. Mondal, D., Zhanel, G.G., Schweizer, F. Synthesis and antibacterial properties of carbohydrate-templated lysine surfactants. Carbohydr. Res. 346, 588-594 (2011).
  8. Bera, S. Zhanel, G.G., Schweizer, F. Synthesis and antibacterial activity of amphiphilic lysine-ligated neomycin B conjugates. Carbohydr. Res. 346, 560-568 (2011).
  9. Fujita, Y., Ohshima, N., Hasegawa, A., Schweizer, F., Takeda, T., Kiuchi, F., Hada, N., Synthesis, inhibitory effects on nitric oxide and structure-activity relationships of a glycosphingolipid from the marine sponge Aplysinella rhax and its analogues. Molecules 16, 637-651 (2011).
  10. Zhanel, G.G., Decorby, M., Adam, H., Mulvey, M.R., McCracken, M., Lagacé-Wiens P., Nichol, K.A., Wierzbowski, A., Baudry P.J., Tailor, F., Larlowsky, J.A., Walkty, A., Schweizer, F., Johnson, J., Hoban D.J. Prevalence of antimicrobial-resistant pathogens in Canadian hospitals: results of the Canadian ward surveillance study (CANWARD 2008). Antimicrobial Agents Chemother. 54, 4684-4693 (2010).
  11. Teklebrhan R.B., Zhang, K., Schreckenbach, G., Schweizer, F., Wetmore, S.D. Intramolecular hydrogen-bond controlled prolyl amide isomerization in glucosyl 3(S)-hydroxy-5-hydroxymethylproline hybrids: a computational study. J. Phys Chem. B 114, 11594-11602 (2010).
  12. Findlay, B., Zhanel, G.G., Schweizer, F. Cationic amphiphiles: a new generation of antimicrobials inspired by the natural antimicrobial scaffold. Antimicrobial Agents Chemother. 54, 4049-4058 (2010).
  13. Kanaya T, Yagi, S., Schweizer, F., Takeda, T., Kiuchi, F., Hada, N. Synthetic studies on glycosphingolipids from protostomia phyla: synthesis of glycosphingolipids from the parasite Schistosoma mansoni. Chem. Pharm. Bull. (Tokyo) 58, 811-817, (2010).
  14. Mondal, D., Schweizer, F. Synthesis of allose-templated hydroxyornithine and hydroxyarginine analogues. Carbohydr. Res. 345, 1533-1540, (2010).
  15. Bera, S., Zhanel, G.G., Schweizer, F. Evaluation of amphiphilic aminoglycoside-peptide triazole conjugates as antibacterial agents. Bioorg. Med. Chem. Lett. 20, 3031-3035 (2010).
  16. Zhang, K., Schweizer, F. Influence of glucose-templated proline mimetics on the b-turn conformation of the peptide fragment Ac-Leu-D-Phe-Pro-Val-NMe2 found in Gramicidin S. Carbohydr. Res. 345, 1114-1122 (2010).
  17. Bera, S, Zhanel, G.G., Schweizer, F. Antibacterial activities of aminoglycoside antibiotics-derived cationic amphiphiles. Polyol-modified neomycin B-, kanamycin A-, amikacin- and neamine-based amphiphiles with potent broad-spectrum antibacterial activity. J. Med. Chem. 53, 3626-3631 (2010).
  18. Owens, N.W., Stetefeld, J., Lattová, E., Schweizer, F. Contiguous O-galactosylation of 4R-hydroxy-L-proline residues forms very stable polyproline II helices. J. Am. Chem. Soc. 132, 5036-5042  (2010).
  19. Bera, S. Zhanel, G.G., Schweizer, F. Antibacterial activity of guanidinylated neomycin B and kanamycin A-derived amphiphilic lipid conjugates. J. Antimicrob. Chemother. 65, 1224-1227 (2010).
  20. Zhanel, G.G., Calic, D., Schweizer, F., Zelenitsky, S., Adam, H., Lagace-Wiens, P.R.S., Rubinstein, E., Gin, A.S., Hoban, D.J., Karlowsky, J.A. Dalbavancin, oritavancin and televancin: A comparative review. Drugs 70, 859-886 (2010).
  21. Hada, N., Shida, Y., Negishi, N., Schweizer, F., Takeda, T. Synthesis of glycoclusters containing a phosphocholine residue related to a glycosphingolipid from the earthworm Pheretima hilgendorfi. Chem. Pharm. Bull. 57, 1081-1088 (2009).
  22. Schweizer, F. Cationic amphiphilic peptides with cancer-selective toxicity. Eur. J. Pharmcol. 625, 190-194 (2009).
  23. Owens, N. W., Lee, A., Marat, K., Schweizer, F. The implications of (2S,4S)-hydroxyproline 4-O-glycosylation for prolyl amide isomerization. Chem. Eur. J. 15, 10649-10657 (2009). 
  24. Zhanel, G.G., DeCorby, M., Nichol, K.A., Wierzbowski, A., Baudry, P., Karlowsky, J.A.,Lagacé-Wiens, P., Walkty, A., Schweizer F., McCracken M, Mulvey M. The Canadian Antimicrobial Resistance Alliance (CARA) and Hoban DJ. Antimicrobial resistant pathogens in Canadian hospitals: results of the Canadian Ward Surveillance Study CANWARD 2007. Can. J. Infect. Dis. & Med. Micro.20 (Suppl A):4-71 (2009).
  25. Zhanel, G.G. Zniezek, G., Schweizer, F., Zelenitsky, S., Lagace-Wiens, R.S., Rubinstein, E., Gin, A,S., Hoban, D.J., Karlowsky, J.A. Ceftaroline: a novel broad-spectrum cephalosporin with activity against meticillin-resistant Staphylococcus aureus. Drugs, 69, 809-831 (2009).
  26. Serrano, G,N., Zhanel, G.G., Schweizer, F. Antibacterial activity of ultrashort cationic lipo-b-peptides. Antimicrobial Agents & Chemother. 53, 2215-2217 (2009).
  27. Koizumi, A., Hada, N., Kaburaki, A., Yamano, K., Schweizer, F., Takeda, T. Synthetic studies on the carbohydrate moiety of the antigen from the parasite Echinococcus multilocularis. Carbohydr. Res. 344, 856-868 (2009).
  28. Zhang, K., Teklebrhan, R.B., Schreckenbach, G., Wetmore, S., Schweizer, F. Intramolecular hydrogen bond-controlled prolyl amide isomerization in glucosyl 3’(S)-hydroxy-5’-hydroxymethylproline hybrids: Influence of a C-5’-hydroxymethyl substituent on the thermodynamics and kinetics of prolyl amide cis/trans isomerization. J. Org. Chem. 74, 3735-3743 (2009).
  29. Zhang, K., Schweizer, F. Design and synthesis of glucose-templated proline-lysine chimera: polyfunctional amino acid chimera with high prolyl cis amide rotamer population. Carbohydr. Res. 344, 576-585 (2009).
  30. Bera, S., Zhanel, G.G., Schweizer, F. Design, synthesis and antibacterial activities of neomycin-lipid conjugates: polycationic lipids with potent gram-positive activity. J. Med. Chem. 51, 6160-6164 (2008).
  31. Mondal, D., Schweizer, F. Alkylation reactions using a galactose-based beta-ketoester enolate and conversion into b-C-galactosides. Synlett 2475-2478 (2008).
  32. Zhang, K., Mondal, D., Zhanel, G.G., Schweizer, F. Synthesis of glucose-templated lysine analogs and incorporation into the antimicrobial dipeptide sequence kW-OBn. Carbohydr. Res. 343, 1644-52 (2008).
  33. Zhanel, G.G., Lam, A., Schweizer, F., Thomson, K., Walkty, A., Rubinstein, E., Gin, A.S., Hoban, D.J., Noreddin, A.M., Karlowsky, J.A. Ceftobiprole: A review of a broad spectrum and anti-MRSA cephalosporin. Am. J. Dermatol. 9, 245-254 (2008).
  34. Owens, N.W., Braun, C., O’Neil, J. D., Marat, K. and Schweizer, F. Effects of glycosylation of (2S,4R)-hydroxyproline on the conformation, kinetics and thermodynamics of prolyl amide isomerization. J. Am. Chem. Soc. 129, 11670-71 (2007).
  35. Schweizer, F. Synthesis of fluorescence-labeled and internally quenched UDP-Gal probes. Carbohydr. Res342, 1831-40 (2007).
  36. Zuse, A, Prinz, H., Mueller, K., Schmidt, P., Guenther, E.G., Schweizer, F, Prehn, J. and Los, M. 9-Benzylidene-naptho[2,3b]thiophen-4-ones and benzylidene-9-(10H)-anthracenones as novel tubulin interacting agents with high apoptosis-inducing activity. Eur. J. Pharm. 575, 34-45 (2007).
  37. Owens, N.W., Braun, C. and Schweizer, F. Tuning of the prolyl trans/cis amide rotamer population by use of C-glucosylproline hybrids. J. Org. Chem. 72, 4635-4643 (2007).
  38. Zhang, K., Wang, J., Sun, Z., Huang, H-D. and Schweizer, F. Synthesis of sugar-lysine chimera with integrated 1,3 hydroxyamine motif. Synlett 239-242  (2007).

 

Book Chapters / Comments

  1. Owens, N.W., Schweizer F. in peptides and glycopeptides, Contemporary Biotechnology 2nd edition, Elsevier pp. 122-138 (2011).
  2. Banerji, S., Ande, R.S. Maddika, S., Banerji, S., Rashedi, I., Owens, N. W., Zuse, A., Schweizer, F and Los, M. Peptides and peptidomimetics as cancer therapy sensitizing agents in “Sensitization of cancer cells for chemo/immuno/radio-therapy” B. Bonavida (Ed.) Humana Press p. 279-304. (2008).
  3. Schweizer F. Carbohydrate Chemistry and Biochemistry by Michael L. Sinnott. Angew. Chem. Intl. Ed. 47, 5969-5697 (2008).
  4. Schweizer, F. Engineering carbohydrate scaffolds into the side chains of amino acids and use in combinatorial synthesis in “Handbook of Carbohydrate Engineering” (K.Y. Yarema ed.) Taylor & Francis, Boca Raton p. 749-780 (2005).

 

Patents / Intellectual Property Rights

  1. Antitumor glycolipids. US Provisional No. US 61/596,415.
  2. Polycationic amphiphiles with cancer selective toxicity. US Provisional No. 61/587,185
  3. Guanidinylated aminoglycoside-lipid conjugates. PCT International Application WO2012004684.
  4. Preparation of polyol modified aminoglycoside-lipid conjugates as antibacterial agents. PCT International Application WO2011124986.
  5. Preparation of carbohydrate-based b-turn mimetics especially glucose-templated proline mimetics. PCT International Application WO2010113035.
  6. Antimicrobial cationic lipo-b-peptides. PCT International Application WO2010109284.
  7. Preparation of hydrophobically enhanced aminoglycosides as antibacterial agents. PCT International Application WO2010004433.
  8. Preparation of triazole-based aminoglycoside-peptide conjugates. PCT International Application WO2009037592. This patent application has also been filed in Canada (CA2687689AA issued), in Europe (EP2167522A2) and US (US20100261639A1).
  9. Synthesis of carbohydrate-templated amino acids and methods of using same. CA 2568954 (issued); US11/857,367 (issued).
  10. Synthesis of carbohydrate-templated amino acids, particularly glucose-lysine chimeras, and their use as coupling components in the preparation of antimicrobial peptides. PCT International Application WO2008035222. This patent has also been filed in Europe (EP2078034A2) and in the US (US20080274213A1).

Dr. Yaozu Xu Postdoctoral Fellow    
Brandon Findlay PhD Student    
Makanjuola Ogunsina PhD Student    
Venkata Murthy MSc Student    
OweBenjamin Eisner Undergraduate Student    
Ronald Domalaon Undergraduate Student