Henrik Franzyk

• M. Sc. Engineering (Chemistry; Cand. polyt.) at The Technical University of Denmark, 1991.
• Ph.D. (Natural Products Chemistry) from The Technical University of Denmark, 1993.

• 1994-1996: Post doc at Carlsberg Laboratory. Peptide, carbohydrate and solid-phase chemistry. Advisor: Adj. Professor Morten Meldal.
• 1996-1997:  Research assistant professor at Dept. Organic Chemistry, The Technical University of Denmark
• 1997:  Post doc at Colorado State University, Fort Collins (six months)    with Professor Frank Stermitz.
• 1998-2000:  Research associate professor at Dept. Organic Chemistry, The Technical University of Denmark.
• 2000- :  Associate professor at Dept. Medicinal Chemistry, The Danish University of Pharmaceutical Sciences.

• The Gorm Petersen Memorial Award (for Ph.D. thesis), 1993.
• Talent Project (3.0 mio. DKK) entitled "Solid-Phase Synthesis of Neuroactive Polyamine Derivatives" from The Technical Research Council (STVF), 2000.
• Carlsberg Foundation, 2001 and 2002 (polyamine research: 150.000 DKK and 160.000 DKK, respectively).
• FSS, 2006 (160.000 DKK) to "Sequence-Structure Investigations and Synthesis of Novel Antimicrobial β-peptoids)".
• Lundbeck Foundation, 2006 (959.306 DKK) to "Aziridine-based Diversity-oriented Synthesis on Solid Phase".
• FSS, 2008 (904.500 DKK) to "Studies Towards CPP-Promoted Macromolecular Drug Delivery".
• FTP, 2008 (3.958.006 DKK) to "Novel Antibiotic Peptidomimetics"
• DSF, 2009 (2.613.600 DKK) as a partner in  the Danish Centre for Antibiotic Research and Development (DanCARD).

At present I am responsible for Bioorganic Chemistry (M23-1) and the associated Laboratory Exercises in Bioorganic Chemistry (M23-2). In addition, I give lectures in spectroscopy in Organic Chemistry II (M22-1).

Previously: supervision of one postdoc and three PhD students; co-supervision of two PhD students as well as supervision of a number of master and scholar students.
Currently: One postdoc, one PhD student and a scholar student; co-supervision of two PhD students and one master student.

• Development of solid-phase methodologies
• Design and optimization of naturally occurring pebtides
• Structure elucidation of natural products
• Synthesis of peptidomimetics

Generally, the research interests comprise total synthesis of biologically active  natural products and optimization of analogues by parallel solid-phase synthesis as well as development of their medicinal chemistry.
Previously, I have been managing a talent project concerning development of novel solid-phase organic chemistry and its application in SAR studies of analogues of the natural product lead philanthotoxin-433 (originating from a wasp); two PhD students were assigned to this project.  Extremely selective and potent analogues have been designed for both glutamate and nACh receptors.
Utilization of aziridine building blocks in diversity-oriented solid-phase synthesis (SPS) have recently been investigated by a PhD student. Novel types of amino acids proved to be accessible by multi-step SPS using aziridines as key intermediates.
Studies towards improved cell-penetrating peptides for macromolecular drug delivery constitute a novel PhD project performed in cooperation with Department for Pharmaceutics and Analytical Chemistry (Assoc. Prof. Hanne M. Nielsen) and Novo Nordisk A/S.
In addition, I am coordinating a project concerning structural studies and pharmacological optimization of a novel type of mimics of natural antimicrobial peptides (AMPs). Novel peptidomimetics composed of alternating α-amino acids and β-peptoid units are investigated as AMP mimics. A recent grant for a joint project with research Groups at DTU (Prof. Lone Gram and Prof. Søren Molin) and SSI (Prof. Niels Frimodt-Møller) allows for in-depth studies of these novel antibacterials.
Recently, I joined  as partner (main supervisor of one PhD)  the Danish Centre for  Antibiotic Research and Development (DanCARD) granted by the Danish Council for Strategic Research (total amount: 31 mio. DKK), which enables further investigations regarding antimicrobial peptides and peptidomimetics.
Finally, a project concerning development of lipid vaccine adjuvants is undertaken by a PhD student in cooperation with Department for Pharmaceutics and Analytical Chemistry (main supervisor: Assoc. Prof Camilla Foged) and Statens Serum Institut (SSI).

Peptide analogues

Collaborators

Total number of  peer-reviewed articles and reviews: 65
Total number of other publications: 9
H-index: 16

Peer-reviewed articles and reviews (last 5 years)

2010
Olsen, C. A.; Ziegler, H. L.; Nielsen, H. M.; Frimodt-Møller, N.; Jaroszewski, J. W.; Franzyk, H. Antimicrobial, Hemolytic, and Cytotoxic Activities of Selective Antimicrobial β-Peptoid-Peptide Hybrid Oligomers.  ChemBioChem 2010, 11, 1356-1360.

Ottesen, L. K.; Jaroszewski, J. W.; Franzyk, H. Ring Opening of a Resin-bound Chiral Aziridine with Phenol Nucleophiles.  J. Org. Chem. 2010, 75, 4983-4991.

Frølund, S.; Kristensen, A.; Ziegler, H.; Olsen, C. A.; Strømgaard, K.; Franzyk, H.; Jaroszewski, J. W. Assessment of Structurally Diverse Philanthotoxin Analogues for Inhibitory Activity on Ionotropic Glutamate Receptor Subtypes: Discovery of Nanomolar, Non-Selective, and Use-Dependent Antagonists. J. Med. Chem. 2010, (accepted - in press).

Nordly, P.;  Korsholm, K. S.;  Pedersen, E. A.;  Khilji, T. S.; Franzyk, H.; Jorgensen, L.;  Nielsen, H. M.;  Agger, E. M.; Foged, C. Incorporation of a Synthetic Mycobacterial Monomycoloyl Glycerol Analogue Stabilizes Dimethyldioctadecylammonium Liposomes and Potentiates their Adjuvant Effect in vivo.  Eur. J. Pharm. Biopharm. 2010, (accepted - in press).

2009
Ottesen, L. K.; Olsen, C. A.; Witt, M.; Jaroszewski, J. W.; Franzyk, H. Selectively N-Protected Enantiopure 2,5-Disubstituted Piperazines: Avoiding the Pitfalls in Solid-Phase Fukuyama-Mitsunobu Cyclizations. Chem., Eur. J. 2009, 15, 2966-2978.

Crestey, F.; Witt, M.; Jaroszewski, J. W.; Franzyk, H. Expedite Protocol for Construction of Chiral Regioselectively N-Protected Monosubstituted Piperazine, 1,4-Diazepane, and 1,4-Diazocane Building Blocks. J. Org. Chem. 2009, 74, 5652-5655.

2008
Olsen, C. A.; Lambert, M.; Witt, M.; Franzyk, H.; Jaroszewski, J. W. Solid-Phase Peptide Synthesis and Circular Dichroism Study of Chiral β-Peptoid Homooligomers. Amino Acids 2008, 34, 465-471.

Crestey, F.; Witt, M.; Frydenvang, K.; Stærk, D.; Jaroszewski, J. W.; Franzyk, H. Microwave-Assisted Ring-Opening of Activated Aziridines with Resin-Bound Amines. J. Org. Chem. 2008, 73, 3566-3569.

Bonke, G.; Vedel, L.; Witt, M.; Jaroszewski, J. W.; Olsen, C. A.; Franzyk, H. Dimeric Building Blocks for Solid-Phase Synthesis of α-Peptide–β-Peptoid Chimeras. Synthesis 2008, 2381-2390.

Foged, C.; Franzyk, H.; Bahrami, S.; Frøkjær, S.; Jaroszewski, J. W.; Nielsen, H. M.; Olsen, C. A. Cellular Uptake and Membrane-Destabilizing Properties of α-Peptide/β-Peptoid Chimeras: Lessons for the design of New Cell-Penetrating Peptides. BBA – Biomembranes 2008, 1778, 2487-2495.

Crestey, F.; Ottesen, L. K.; Jaroszewski, J. W.; Franzyk, H. Efficient Loading of Primary Alcohols onto a Solid Phase Using a Trityl Bromide Linker. Tetr. Lett. 2008, 49, 5890-5893.

2007
Olsen, C. A.; Witt, M.; Franzyk, H.; Jaroszewski, J. W. Solid-Phase Synthesis of Neuroactive Spider-Wasp Hybrid Toxin Analogues Using a Backbone Amide Linker. Tetr. Lett. 2007, 48, 405-408.

Olsen, C. A.; Bonke, G.; Vedel, L.; Adsersen, A.; Witt, M.; Franzyk, H.; Jaroszewski, J. W. α-Peptide/β-Peptoid Chimeras. Org. Lett. 2007, 9, 1549-1552.

Olsen, C. A.; Franzyk, H.; Jaroszewski, J. W. Aziridines in Parallel- and Solid-Phase Synthesis. Eur. J. Org. Chem. 2007, 1717-1724.

Vedel, L.; Bonke, G.; Foged, C.; Ziegler, H.; Franzyk, H.; Jaroszewski, J. W.; Olsen, C. A. Antiplasmodial and Prehemolytic Activities of α-Peptide–β-Peptoid Chimeras. ChemBioChem 2007, 8, 1781-1784.

2006
Olsen, C. A.; Mellor, I. R.; Wellendorph, P.; Usherwood, P. N. R.; Witt, M.; Franzyk, H.; Jaroszewski, J. W. Tuning Wasp Toxin  Structure for Nicotinic Receptor Antagonism: Cyclohexylalanine-Containing Analogues as Potent and Voltage-Dependent Blockers. ChemMedChem 2006, 1, 303-305. 

Olsen, C. A.; Christensen, C.; Nielsen, B.; Mohamed F. M.; Witt, M.; Clausen, R. P.; Kristensen, J. L.; Franzyk, H.; Jaroszewski, J. W. Aminolysis of Resin-Bound N-Nosylaziridine-2-carboxylic Acids. Org. Lett. 2006, 8, 3372-3374.

Strømgaard, K.; Piazzi, L.; Olsen, C. A.; Franzyk, H.; Jaroszewski, J. W. Protolytic Properties of Polyamine Wasp Toxin Analogues Studied by ¹³C NMR Spectroscopy. Magn. Reson. Chem. 2006, 44, 1013-1022.

2005
Jørgensen, M. R.; Olsen, C. A.; Mellor, I. R.; Usherwood, P. N. R.; Witt, M.; Jaroszewski, J. W.; Franzyk, H. The Effects of Conformational Constraints and Steric Bulk in the Amino Acid Moiety of Philanthotoxins on AMPAR Antagonism. J. Med. Chem. 2005, 48, 56-70.

Jaroszewski, J. W.; Stærk, D.; Holm-Møller, S. B.; Jensen, T. H.; Franzyk, H.; Somanadhan, B. Naravelia Zeyanica: Occurrence of Primary Benzamides in Flowering Plants. Nat. Prod. Res. 2005, 19, 291-194.

Olsen, C. A.; Jørgensen, M. R.; Hansen, S. H.; Witt, M.; Jaroszewski, J. W.; Franzyk, H. Side-Chain-Anchored N^α-Fmoc-Tyr-OPfp for Bidirectional Solid-Phase Synthesis. Org. Lett. 2005, 7, 1703-1706.

Olsen, C. A.; Witt., M.; Hansen, S. H.; Jaroszewski, J. W.; Franzyk, H. Fukuyama-Mitsunobu Alkylation in Amine Synthesis on Solid Phase Revisited: N-Alkylation with Secondary Alcohols and Synthesis of Curtatoxins. Tetrahedron 2005, 61, 6046-6055.

Olsen, C. A.; Jaroszewski, J. W.; Franzyk, H. N-Alkylation Reactions and Indirect Formation of Amino Functionalities in Solid-Phase Synthesis. Synthesis 2005, 2631-2653.

Jørgensen, M. R.; Jaroszewski, J. W.; Witt, M.; Franzyk, H. On-resin Carboxy Group Activation of ω-Amino Acids in Solid-Phase Synthesis of Philanthotoxin Analogues. Synthesis 2005, 2687-2694.

Other publications
Olsen, C. A.; Franzyk, H.; Jaroszewski, J. W. Nanomolær inhibering med hvepsetoksinanaloger – syntese og elektrofysiologi. Dansk Kemi 2006, 87, 23-26.

Crestey, F.; Witt, M.; Frydenvang, K.; Stærk, D.; Jaroszewski, J. W.; Franzyk, H. Microwave-Assisted Ring-Opening of Activated Aziridines with Resin-Bound Amines. Synfacts 2008, 7, 769. (summary of J. Org. Chem. 2008, 73, 3566-3569).

Jaroszewski, J. W.; Christensen, S. B.; Franzyk, H.; Stærk, D.; Ziegler, H. Lægemidler fra naturstoffer: fortid eller fremtid. Lægemiddelforskning 2008, pp 4-6