Henrik Franzyk

Henrik Franzyk

Associate Professor

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

See also website for the research group Peptide-based Drug Research:


See also website for the research cluster Cancer and Infectious Diseases:



Current projects are supported by Novo Nordisk Foundation (Challenge project partnership: Center for Peptide-Based Antibiotics), Norwegian Research Council (co-PI in: A platform for development of peptide-based antimicrobials for treatment of infections with drug-resistant bacteria, and The Danish Research Council (DFF1 project: Exploration of efflux pump inhibitor conjugates via Trojan-horse and shuttle approaches).

The main scientific outcome during 2018-2023 concerns the following:

(i) Potent antimicrobial peptides (AMPs) and antibacterial peptidomimetics with activity against multidrug-resistant (MDR) bacteria.

(ii) Design and synthesis of antisense PNA-peptide conjugates (e.g., AMPs covalently linked to peptide nucleic acid oligomers). 

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

(iv) Development of improved methodologies in solid-phase synthesis (SPS) of peptidomiumetics and on-resin modification of peptides.

(v) 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 2018-2023 these studies have been published in 49 articles in peer-reviewed journals together with 12  other publications. Currently, HF has published 173 peer-reviewed articles and monographies, 2 book chapters, and 88 other research contributions (e.g., patents, popular science communications, proceedings, and posters).


Bibliometric data:

h-index:               34 (Web of Science);  40 (Google Scholar)

i10-index:            121 (Web of Science); 133 (Google Scholar)

Citations:             3925 (cf. Web of Science – search in all databases);

                             5235 (cf. Google Scholar)


Primary fields of research

(i) SAR studies of peptide-based/peptidomimetic antibacterial compounds as well as potentiators and conjugates of antibiotics;

(ii) Bacterial delivery of antibiotics (including AMPs and antisense PNA oligomers);

(iii) Improved macromolecular drug delivery (targeting peptides and cationic lipids for nanoparticles with siRNA/mRNA; lipid adjuvants for vaccines);

(iv) Mechanisms and structural optimization of immunomodulating peptides and peptidomimetics;

(v) Solid-phase synthesis method development



(i) Biopharmaceuticals: Bioorganic Chemistry (theory and exercises; course director)

(ii) Postdoctoral, PhD, MSc and BSc projects within design of antimicrobial compounds, peptide chemistry, drug conjugates, and solid-phase synthesis methods



Current research




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

In response to the critically 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 and/or intracellular target(s).

Membrane-permeabilizing adjuvant antibiotics have been discovered and investigated as a means for circumventing resistance to current antibiotics and to sensitize bacteria to antibiotics that they are inherently resistant to. Also, synergistic combinations representing a multimodal treatment regimen are examined as an approach for reducing risk of resistance development. In addition, novel peptide carriers for efficient bacterial uptake of potential antibacterial compounds (e.g., antisense PNA oligomers) have been explored. Ongoing studies concern development of novel cyclic lipopeptide antibiotics (e.g., analogues of colistin) as well as optimization of peptidomimetics exerting bacterial killing and/or adjuvant effects when combined with existing antibiotics.

Center for Peptide-Based Antibiotics (CEPAN) is funded by an NNF Challenge grant and headed by Prof. P.E. Nielsen (Dept. Cellular and Molecular Medicine, University of Copenhagen). See more at: http://cepan.ku.dk

Group members (in the Franzyk lab) comprise: Previous (Postdocs/PhD student): Anita Wester (Delivery moieties for antibacterial antisense PNA oligomers), Ashif Yasin Shaikh (PNA synthesis and antibiotic-peptide conjugates), and Nicki Frederiksen (Antimicrobial peptides and peptidomimetics); current (PhD student): Johan Storm Jørgensen (Novel cyclic lipopeptide antibiotics).

Selected publications:

Frederiksen, N.; Loukas, S.; Mudaliar, C.; Domraceva, I.; Kreichberga, A.; Pugovics, O.; Zabicka, D.; Tomczak, M.; Wygoda, W.; Björkling, F.; Franzyk, H. Peptide/β-Peptoid hybrids with ultrashort PEG-like moieties: Effects on hydrophobicity, antibacterial and hemolytic properties. Int. J. Mol. Sci. 2021, 22, 7041 (17 pages). https://doi.org/10.3390/ijms22137041

Mood, E. H.; Goltermann, L.; Brolin, C.; Cavaco, L. M.; Yavari, N.; Frederiksen, N.; Nejad, A. J.;  Franzyk, H.; Nielsen, P. E. Antibiotic potentiation in multidrug-resistant Gram-negative pathogenic bacteria by a synthetic peptidomimetic. ACS Infect. Dis. 2021, 7, 2152-2163. https://doi.org/10.1021/acsinfecdis.1c00147

Frederiksen, N; Hansen, P. R.; Zabicka, D.; Tomczak, M.; Urbas, M.; Domraceva, I.; Björkling, F.; Franzyk, H. Peptide/peptoid hybrid oligomers: The influence of hydrophobicity on antibacterial activity and cell selectivity. ChemMedChem 2020, 15, 2544-2561. https://doi.org/10.1002/cmdc.202000526

Frederiksen, N; Hansen, P. R.; Björkling, F.; Franzyk, H. Peptide/peptoid hybrid oligomers: Influence of hydrophobicity and relative side-chain length on antibacterial activity and cell selectivity. Molecules 2019, 24, 4429 (18 pages). https://doi.org/10.3390/molecules24244429

Contact: Henrik Franzyk; henrik.franzyk@sund.ku.dk


A platform for development of peptide-based antimicrobials for treatment of infections with drug-resistant bacteria (Norwegian Research Council; Project leader: M. Bjørås; co-PI: H. Franzyk).

A worldwide health crisis is emerging as Gram-negative bacteria are becoming multidrug-resistant (MDR), leaving them to be treated with last-resort antibiotics only. As the pharmaceutical industry’s discovery and development of novel antibiotics often are based on existing compound classes, resistance often develops rapidly. This troublesome approach calls for academia to perform alternative research within future antibiotics.

Focus in the present project is on design and synthesis of compounds based on modification of newly identified hit peptides arising from the toxin part of bacterial toxin-antitoxin systems. The aim is to improve bacterial uptake, while minimizing toxicity toward mammalian cells. Also, incorporation of unnatural residues is used as a means to increase stability towards enzymatic degradation in vivo. Emphasis will be on identification and development of lead compounds against Gram-negative human pathogens (e.g., E. coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa).

PhD student: Emma Dyhr Jensen (Project title: Exploration of peptides derived from the bacterial toxin-antitoxin system as potential antibiotics)

Selected publications:

Sæbø, I. P.; Bjørås, M.; Franzyk, H.; Helgesen, E.; Booth, J. A. Optimisation of the hemolysis assay for the assessment of cytotoxicity. Int. J. Mol. Sci. 2023, 24, 2914 (20 pages).

Contact: Henrik Franzyk; henrik.franzyk@sund.ku.dk


Exploration of efflux pump inhibitor conjugates via Trojan-horse and shuttle approaches (The Danish Research Council; DFF1 project granted to H. Franzyk).

Multidrug-resistant (MDR) Gram-negative bacteria cause infections only treatable with last-resort antibiotics. Overexpression of efflux pumps is a common trait of most MDR strains, and thus it is the aim to explore novel approaches for efficient bacterial delivery of efflux pump inhibitors (EPIs), capable of restoring sensitivity to antibiotics. This comprises design and synthesis of conjugates with uptake-promoting moieties, which is hypothesized to constitute a viable means to obtain such adjuvant antibiotics. A major aim is to reduce toxicity and off-target effects of the current most efficient EPIs that include drug candidates developed for treatment of other diseases. A successful project outcome is compounds that enable resensitization of MDR strains and repurposing of existing antibiotics with profound impact for patients and society.

PhD student: Mikkel Stampe Madsen

Contact: Henrik Franzyk; henrik.franzyk@sund.ku.dk


Springboard (Coordination and support action under the H2020-WIDESPREAD-2018-2020 call; Coordinator: Latvian Institute of Organic Synthesis,Riga; co-PI: Henrik Franzyk)

The main goal of the SPRINGBOARD project is to strengthen the research potential of the Latvian Institute of Organic Synthesis (LIOS) through establishing long-lasting and sustainable network collaborations with leading European research institutions (University of Antwerp, University of Copenhagen, University of Florence and University of Helsinki) in the area of advanced discovery of novel antibacterial drugs. This includes competence strengthening within biopharmaceuticals such as peptide-based antibiotics, and has so far involved design and solid-phase synthesis (SPS) of dimeric building blocks and on-resin modification of amino functionalities in a 12-mer peptidomimetic to obtain a series of novel peptidomimetics displaying an unprecendented content of unusual side chains. Another part comprises a series of end-group modified peptidomimetics.

Plotniece, A.; Soboleva, A.; Supuran, C. T.; Carta, F.; Björkling, F.; Franzyk, H.; Yli-Kauhaluoma, J.; Augustyns, K.; Cos, P.; De Vooght, L.; Govaerts, M.; Aizawa, J.; Tammela, P.; Žalubovskis, R. Selected strategies to fight pathogenic bacteria. J. Enz. Inhib. Med. Chem. 2023, 38, 21554816 (27 pages). https://doi.org/10.1080/14756366.2022.2155816


ENABLE (European Gram-negative Antibacterial Engine - an Innovative Medicines programme;  EU-funded 2015-2021; co-PI: H. Franzyk)

Antimicrobial resistance (AMR) is a major public health threat 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 aim of the ENABLE project, within IMI’s New Drugs for Bad Bugs (ND4BB) programme, was to advance the development of potential antibiotics against Gram-negative bacteria, such as Escherichia coli. The ultimate goal of the individual projects were to develop attractive antimicrobial candidates for testing in the clinic.  

Selected publications:

Hansen, A. M.; Bonke, G.; Hogendorph, W. F. J.; Björkling, F.; Nielsen, J.; Nielsen, P. E.; Kongstad, K. T.; Zabicka, D.; Franzyk. H. Microwave-assisted solid-phase synthesis of antisense acpP peptide nucleic acid-peptide conjugates active against colistin- and tigecycline-resistant E. coli and K. pneumoniae. Eur. J. Med. Chem. 2019, 168, 134-145. https://doi.org/10.1016/j.ejmech.2019.02.024

Hansen, A. M.; Seigan, G. B.; Larsen, C. J.; Yavari, N.; Nielsen, P. E.; Franzyk, H. Antibacterial peptide nucleic acid − antimicrobial peptide (PNA-AMP) conjugates: Antisense targeting of fatty acid biosynthesis. Bioconjugate Chem. 2016, 27, 863-867. https://doi.org/10.1021/acs.bioconjchem.6b00013

Contact: Henrik Franzyk; henrik.franzyk@sund.ku.dk





Prof. Claus E. Moser, Dept. Clinical Microbiology, Rigshospitalet (Copenhagen University Hospital)

Prof. Anders Løbner-Olesen, Dept. Biology, University of Copenhagen

Prof. Peter E. Nielsen, Dept. Cellular & Molecular Biology, University of Copenhagen

Prof. Luca Guardabassi, Dept. Veterinary & Animal Sciences, University of Copenhagen

Prof. Hanne Ingmer, Dept. Veterinary & Animal Sciences, University of Copenhagen

Prof. Camilla Foged, Dept. Pharmacy, University of Copenhagen

Statens Serum Institut (several senior scientists)



Prof. Magnar Bjørås, Dept. Microbiology, Oslo University Hospital, Norway & Dept. Cancer Research & Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway

Prof. Fernando Rogério Pavan, Sao Paulo State University, Sao Paolo, Brazil

Assoc. Prof. Liam Good, Pathobiology & Population Science, Royal Veterinary College, London, U.K.

Assoc. Prof. Lorenzo Stella, Dept. Chemical Science and Technologies, University of Rome Tor Vergata, Rome, Italy

Prof. Maria Luisa Mangoni, Dept. Biochemical Sciences, Sapienza University of Rome, Rome, Italy

Dr. Dorota Zabicka, National Microbiology Institute, Warzaw, Poland

Director, O. Pugovics, Latvian Institute of Organic Synthesis, Riga, Latvia

Dr. Ilona Domraceva, Latvian Institute of Organic Synthesis, Riga, Latvia

Prof. Raivis Zalubovskis, Latvian Institute of Organic Synthesis, Riga, Latvia

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

Prof. Claes Dahlgren, Sahlgrenska Academy, University of Gothenburg, Sweden

Assoc. Prof. Ian Mellor, School of Life Sciences, University of Nottingham, U.K.

Assoc. Prof. Izuddin Fahmy Abu, Institute of Medical Science Technology, Universiti Kuala Lumpur, Kuala Lumpur, Malaysia 


Selected publications

  1. Published

    Optimization of the Hemolysis Assay for the Assessment of Cytotoxicity

    Sæbø, I. P., Bjørås, M., Franzyk, Henrik, Helgesen, E. & Booth, J. A., 2023, In: International Journal of Molecular Sciences. 24, 3, 20 p., 2914.

    Research output: Contribution to journalJournal articlepeer-review

  2. Published

    Inoculum effect of antimicrobial peptides

    Loffredo, M. R., Savini, F., Bobone, S., Casciaro, B., Franzyk, Henrik, Mangoni, M. L. & Stella, L., 2021, In: Proceedings of the National Academy of Sciences of the United States of America. 118, 21, 10 p., e2014364118.

    Research output: Contribution to journalJournal articlepeer-review

  3. Published

    Efficacy of natural antimicrobial peptides versus peptidomimetic analogues: a systematic review

    Hellewell, L., Gilani, N. M., Stanton, C. J., Pelligand, L., Franzyk, Henrik, Guardabassi, Luca & Good, L., 2022, In: Future Medicinal Chemistry. 14, 24, p. 1899–1921

    Research output: Contribution to journalReviewpeer-review

  4. Published

    Targeting Toxins toward Tumors

    Franzyk, Henrik & Christensen, Søren Brøgger, 2021, In: Molecules. 26, 5, 23 p., 1292.

    Research output: Contribution to journalJournal articlepeer-review

  5. Published

    In vivo Anti-inflammatory Activity of Lipidated Peptidomimetics Pam-(Lys-βNspe)6-NH2 and Lau-(Lys-βNspe)6-NH2 Against PMA-Induced Acute Inflammation

    Wu, B. C., Skovbakke, S. L., Masoudi, H., Hancock, R. E. W. & Franzyk, Henrik, 2020, In: Frontiers in Immunology. 11, 11 p., 2102.

    Research output: Contribution to journalJournal articlepeer-review

  6. Published

    Peptide/β-Peptoid Hybrids with Activity against Vancomycin-Resistant Enterococci: Influence of Hydrophobicity and Structural Features on Antibacterial and Hemolytic Properties

    Vestergaard, M., Skive, Bolette, Domraceva, I., Ingmer, Hanne & Franzyk, Henrik, 2021, In: International Journal of Molecular Sciences. 22, 11, 5617.

    Research output: Contribution to journalJournal articlepeer-review

  7. Published

    Alternating Cationic-Hydrophobic Peptide/Peptoid Hybrids: Influence of Hydrophobicity on Antibacterial Activity and Cell Selectivity

    Frederiksen, N., Hansen, Paul Robert, Zabicka, D., Tomczak, M., Urbas, M., Domraceva, I., Björkling, Fredrik & Franzyk, Henrik, 2020, In: ChemMedChem. 15, 24, p. 2544-2561

    Research output: Contribution to journalJournal articlepeer-review

  8. Published

    Peptide/Peptoid Hybrid Oligomers: The Influence of Hydrophobicity and Relative Side-Chain Length on Antibacterial Activity and Cell Selectivity

    Frederiksen, N., Hansen, Paul Robert, Björkling, Fredrik & Franzyk, Henrik, 4 Dec 2019, In: Molecules (Print Archive Edition). 24, 18 p., 4429.

    Research output: Contribution to journalJournal articlepeer-review

  9. Published

    Repurposing Azithromycin and Rifampicin Against Gram-Negative Pathogens by Combination With Peptidomimetics

    Baker, K. R., Jana, B., Hansen, A. M., Nielsen, Hanne Mørck, Franzyk, Henrik & Guardabassi, Luca, 2 Jul 2019, In: Frontiers in Cellular and Infection Microbiology. 9

    Research output: Contribution to journalJournal articlepeer-review

  10. Published

    19F-substituted amino acids as an alternative to fluorophore labels: monitoring of degradation and cellular uptake of analogues of penetratin by 19F NMR

    Christensen, M. V., Kongstad, Kenneth Thermann, Sondergaard, T. E., Stærk, Dan, Nielsen, Hanne Mørck, Franzyk, Henrik & Wimmer, R., 2019, In: Journal of Biomolecular N M R. 73, p. 167-182

    Research output: Contribution to journalJournal articlepeer-review

ID: 1302063