Forskning ved Københavns Universitet - Københavns Universitet

Forside
Henrik Franzyk

Henrik Franzyk

Lektor

Henrik Franzyk (HF) has for more than 15 years designed and synthesized biologically active peptides and peptidomimetics as well as glycolipids, polyamines and cationic lipids (used as components for drug delivery and nanoparticles). In addition, HF has performed optimization of several lead structures via medicinal chemistry.

Current projects are supported by Novo Nordisk Foundation (Challenge project partnership: Center for Peptide-Based Antibiotics), EU (IMI project: ENABLE) and The Danish Research Council (DFF).

The scientific outcome during 2013-2017 comprise identification and characterization of:

(i) Potent antibacterial peptidomimetics with activity against multidrug-resistant (MDR) bacteria and biofilm;

(ii) Antimicrobial activity of AMP-PNA conjugates (i.e. antimicrobial peptides covalently linked to peptide nucleic acid oligomers);

(iii) Immunomodulatory peptidomimetics capable of LPS- and LTA-neutralization as well as with nanomolar agonistic and antagonistic selective effects on formyl peptide receptor 2 (FPR2); 

(iv) Components for liposomal and nanoparticular drug formulations, e.g. of siRNA aiming at silencing of genes (or the resulting mRNA) involved in chronic diseases. 

During 2013-2017 these studies have been published in 43 articles in peer-reviewed journals. Currently, HF has in total published 113 peer-reviewed articles and monographies, 2 book chapters, and 62 other research contributions (e.g. popular science communications, proceedings, and posters).

 

Bibliometric data: 

h-index: 25 (Web of Science);  27 (Google Scholar)

i10-index: 59 (Web of Science); 70 (Google Scholar).   

Primære forskningsområder

Design, synthesis and optimization of biologically active compounds:

  • Structure-activity studies of antibacterials and potentiators of antibiotics;
  • Bacterial delivery of antisense antibiotics (peptide-PNA conjugates)
  • Mechanisms and structural optimization of immunomodulating peptides and peptidomimetics;
  • Studies of cell-penetrating peptides for macromolecular drug delivery;
  • Synthesis of unnatural amino acid and peptidomimetic building blocks.

 

Undervisnings- og vejledningsområder

  • Biopharmaceuticals: Bioorganic Chemistry (theory and excercises; course director)
  • Biopharmaceuticals: Chemical Design and Modification of Biomacromolecules (course director)

 

 

Aktuel forskning

Partnership in Center for Peptide-Based Antibiotics (Cepan):

In response to the critical and increasing worldwide threat to human health posed by emergence of bacterial resistance to currently used antibiotics, the overall aim of the center is to establish a discovery platform that focuses on peptide-based antibiotics by exploiting unleashed advantages of peptides that interact with the bacterial envelope. Discovery of leads, therapeutic strategies and antibiotic targets useful for treatment of multidrug-resistant Gram-negative infections, and elucidation of mechanism of action are core activities.

In particular, the antisense antibacterial concept and novel peptide carriers for efficient delivery of potential antibacterial compounds with inherently poor bacterial uptake will be explored. Peptide-based adjuvant antibiotics will be discovered and investigated as a means for circumventing resistance to current antibiotics and to sensibilize bacteria to antibiotics that they are inherently resistant to. Also, synergistic combinations representing a multimodal treatment regimen will be examined as an approach for reducing risk of resistance development.

See more at: http://cepan.ku.dk/

Postdoc:

Anita Wester (Delivery moieties for antibacterial antisense peptide nucleic acid oligomers)

PhD student:

Nicki Frederiksen (Antimicrobial peptides and peptidomimetics as potential antibiotics)

Lab technician:

Uraiwan Adamsen 

 

ENABLE (European Gram-negative Antibacterial Engine - an Innovative Medicines programme):

Antimicrobial resistance (AMR) is a major public health threat. Infections caused by resistant bacteria are increasing and causing Europe to face soaring costs both in terms of lives and public health expenditure. Despite the strong need for new antimicrobials, very few new, effective antibiotics have been brought to the market in the last decades. The ENABLE project, within IMI’s New Drugs for Bad Bugs (ND4BB) programme, is working to advance the development of potential antibiotics against Gram-negative bacteria, such as Escherichia coli. The ultimate goal of the project is to develop attractive antimicrobial candidates for testing in the clinic, bringing the possibility of new antibiotics to treat Gram-negative infections one step closer to patients.  

Postdoc:

Anna Mette Hansen (medicinal chemistry of antibacterial lead structures)

 

Quantitative 19F NMR technology for analysis of complex biological matrices from cellular uptake studies: optimization of delivery of biologics using peptide-based delivery systems (FTP project: Collaboration with Dan Stærk, Kenneth T. Kongstad and main applicant Hanne M. Nielsen)

PhD student:

Malene V. Christensen (Use of a 19F NMR-HPLC-MS hyphenated methodology to investigate the stability, fate and uptake of CPPs) 

 

National collaborators (all projects):

Peter E. Nielsen, Prof. Dept. Cellular and Molecular Biology, KU);

Anders Løbner-Olesen (Prof. Biology, KU);

Peter P. Damborg (Assoc. Prof., IVS, KU);

Statens Serum Institut (several senior scientists);

Dept. Pharmacy (Prof. Hanne M. Nielsen and Assoc. Prof. Camilla Foged; KU);

Lone Gram (Prof. Systems Biology, DTU);

Peter M. H. Heegaard (Prof. Immunology, DTU-VET);

 

International collaborators:

Claes Dahlgren, Sahlgrenska Academy, University of Gothenburg, Sweden;

R. E. W. Hancock, University of British Columbia, Vancouver, Canada;

Luca Guardabassi, Ross University School of Veterinary Medicine, St. Kitts;

Ian Mellor, University of Nottingham. 

Udvalgte publikationer

  1. Udgivet

    End Group Modification: Efficient Tool for Improving Activity of Antimicrobial Peptide Analogues towards Gram-Positive Bacteria

    Jahnsen, R. O., Sandberg-Schaal, A., Frimodt-Møller, N., Nielsen, H. M. & Franzyk, H. 23 jan. 2015 I : European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V. 95, Part A, s. 40–46 7 s.

    Publikation: Forskning - peer reviewTidsskriftartikel

  2. Udgivet

    Lipidated α-Peptide/β-Peptoid Hybrids with Potent Anti-inflammatory Activity

    Skovbakke, S. L., Larsen, C. J., Heegaard, P. M. H., Moesby, L. & Franzyk, H. 2015 I : Journal of medicinal chemistry. 58, 2, s. 801-813 13 s.

    Publikation: Forskning - peer reviewTidsskriftartikel

  3. Udgivet

    Nanoparticle-mediated delivery of the antimicrobial peptide plectasin against Staphylococcus aureus in infected epithelial cells

    Water, J. J., Smart, S., Franzyk, H., Foged, C. & Nielsen, H. M. 18 feb. 2015 I : European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V. 92, s. 65-73 9 s.

    Publikation: Forskning - peer reviewTidsskriftartikel

  4. Udgivet

    Tailoring Cytotoxicity of Antimicrobial Peptidomimetics with High Activity against Multidrug-Resistant Escherichia coli

    Jahnsen, R. D., Sandberg-Schaal, A., Vissing, K. J., Nielsen, H. M., Frimodt-Møller, N. & Franzyk, H. 20 mar. 2014 I : Journal of medicinal chemistry. 57, 7, s. 2864-2873

    Publikation: Forskning - peer reviewTidsskriftartikel

  5. Udgivet

    Characterization of a proteolytically stable multifunctional host defense peptidomimetic

    Jahnsen, R. D., Haney, E. F., Franzyk, H. & Hancock, R. E. W. 10 okt. 2013 I : Chemistry & biology. 20, 10, s. 1286-1295 10 s.

    Publikation: Forskning - peer reviewTidsskriftartikel

  6. Udgivet

    Antimicrobial activity of peptidomimetics against multidrug-resistant Escherichia coli: a comparative study of different backbones

    Jahnsen, R. D., Frimodt-Møller, N. & Franzyk, H. 2012 I : Journal of Medicinal Chemistry. 55, 16, s. 7253-61 9 s.

    Publikation: Forskning - peer reviewTidsskriftartikel

ID: 1302063