Henrik Franzyk

Short presentation

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 2015-2019 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 drug delivery and nanoparticular drug formulations, e.g. of siRNA aiming at silencing of genes (or the resulting mRNA) involved in chronic diseases. 

During 2015-2019 these studies have been published in 60 articles in peer-reviewed journals. Currently, HF has in total published 140 peer-reviewed articles and monographies, 2 book chapters, and 78 other research contributions (e.g. patents, popular science communications, proceedings, and posters).

Bibliometric data: 

h-index: 28 (Web of Science);  32 (Google Scholar)

i10-index: 88 (Web of Science); 96 (Google Scholar).   

Primary fields of research

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.

Teaching

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

Current research

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/

Postdocs:

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

Ashif Yasin Shaikh (building blocks for PNA synthesis, and optimization of MW-assisted PNA synthesis)

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. 

CV

Education     

• 1991: MSc. Engineering (Chemistry), The Technical University of Denmark (DTU).
• 1993: PhD (Natural Products Chemistry), DTU.

Employments

• 1993: Researcher, FeF Chemicals A/S.
• 1994-1996: Postdoc at Carlsberg Laboratory. Peptide, carbohydrate and solid-phase chemistry (with Prof. Morten Meldal).
• 1996-1997: Research assistant professor, Dept. Organic Chemistry, DTU.
• 1997: Postdoc at Colorado State University, Fort Collins (June-December).
• 1998-2000: Research associate professor, Dept. Organic Chemistry, DTU.
• 2000- : Associate professor, Dept. Drug Design and Pharmacology Pharmacology (formerly Dept. Medicinal Chemistry), Faculty of Health and Medical Sciences, University of Copenhagen.