Department of Cellular and
Molecular Medicine

PE Nielsen Group

The research interests of PE Nielsen Group are centered around the DNA mimic PNA (peptide nucleic acid), and the chemical biology and medicinal chemistry properties and applications of derivatives of this molecule.

Research interests

The research interests are centered around the DNA mimic PNA (peptide nucleic acid), and the chemical biology and medicinal chemistry properties and applications of derivatives of this molecule. This includes drug discovery (antisense antibiotics, muscular dystrophy, cystic fibrosis), gene targeting and antisense principles in general and cellular and in vivo delivery and administration of biopharmaceuticals. Additional interests cover origin of life prebiotic systems and the effects of oxidative stress on cellular RNA.

Current project areas

Discovery of PNA and peptide based antibiotics against resistant Gram-negative bacterial infections
Quorum sensing inhibitors as cystic fibrosis drugs
Antisense drugs for Duchenne muscular dystrophy Funded by DFF
Antisense drug delivery and in vivo administration

Selected publications

New Publications

Frederiksen N, Hansen PR, Björkling F, Franzyk H. Peptide/Peptoid Hybrid Oligomers: The Influence of Hydrophobicity and Relative Side-Chain Length on Antibacterial Activity and Cell Selectivity. Molecules 2019, 24, 4429; doi:10.3390/molecules24244429
Goltermann L, Yavari N, Zhang M, Ghosal A, Nielsen PE. PNA Length Restriction of Antibacterial Activity of Peptide-PNA Conjugates in Escherichia coli Through Effects of the Inner Membrane. Front Microbiol. 2019 May 24;10:1032.
Hansen AM, Bonke G, Hogendorf WFJ, Björkling F, Nielsen J, Kongstad KT, Zabicka D, Tomczak M, Urbas M, Nielsen PE, 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 Apr 15;168:134-145.

Selected Publications

Montagner G, Bezzerri V, Cabrini G, Fabbri E, Borgatti M, Lampronti I, Finotti A, Nielsen PE, Gambari R. An antisense peptide nucleic acid against Pseudomonas aeruginosa inhibiting bacterial-induced inflammatory responses in the cystic fibrosis IB3-1 cellular model system. Int J Biol Macromol. 2017 Jun;99:492-498.
Carattoli A, E. Zankari, A. Garcìa-Fernandez, M. Volby Larsen, O. Lund, L. Villa, F.M. Aarestrup, H. Hasman. 2014. Antimicrob Agents Chemother. 58:3895-903.
Charbon, G., Bjørn, L., Chamizo, B.M., Frimodt-Møller, J., and Løbner-Olesen, A. 2014. Nucleic Acids Res.,42, 13228-13241.
Ndeboko B, Narayan R, Lemamy GJ, Jamard C, Nielsen PE, Cova L. Role of cell-penetrating peptides in intracellular delivery of peptide nucleic acids targeting hepadnaviral replication. Molecular Therapy - Nucleic Acids 2017
Hansen, A. M., G. Bonke, C. J. Larsen, N. Yavari, P. E. Nielsen, and H. Franzyk. Antibacterial Peptide Nucleic Acid-Antimicrobial Peptide (PNA-AMP) Conjugates: Antisense Targeting of Fatty Acid Biosynthesis. Bioconjugate Chemistry 2016 27, 863-7.
Brolin, C; Shiraishi, T; Hojman, P.; Krag, TO , Nielsen, PE and Julie Gehl, J. Electroporation Enhanced Effect of Dystrophin Splice Switching PNA Oligomers in Normal and Dystrophic Muscle. Molecular Therapy—Nucleic Acids 2015, 4, e267.
Valero,J . Dr. Shiraishi, T.; Mendoza, J.; Nielsen, P. E. Cellular Antisense Activity of PNA--Oligo(bicycloguanidinium) Conjugates Forming Self-Assembled Nanoaggregates. ChemBioChem 2015 16, 1593-600
Singhal A, Nielsen PE. Cross-catalytic peptide nucleic acid (PNA) replication based on templated ligation. Org Biomol Chem. 2014,12, 6901-7
Nørregaard, K¸ Andersson, M.; Sneppen, K.; Nielsen, P.E.; Brown, S.; , Oddershede, L.B. DNA supercoiling enhances cooperativity and efficiency of an epigenetic switch Proc Natl Acad Sci USA 2013, 110, 17386-91
Ghosal, A.; Vitali, A.; Stach, J. E.; Nielsen, P. E. Role of SbmA in the Uptake of Peptide Nucleic Acid (PNA)-Peptide Conjugates in E. Coli. ACS Chemical Biology. 2013, 8, 360-7
Ghosal, A.; Nielsen, P. E. Potent Antibacterial Antisense Peptide-Peptide Nucleic Acid Conjugates Against Pseudomonas aeruginosa. Nucleic Acid Therapy 2012, 22, 323-334.
Shiraishi, T.; Nielsen, P. E. Nanomolar Cellular Antisense Activity of Peptide Nucleic Acid (PNA) Cholic Acid ("Umbrella") and Cholesterol Conjugates Delivered by Cationic Lipids. Bioconjugate Chemistry 2012, 23, 196-202.
Good, L.; Awasthi, S. K.; Dryselius, R.; Larsson, O.; Nielsen, P. E. Bactericidal Antisense Effects of Peptide-PNA Conjugates. Nature Biotechnology 2001, 19, 360-364.
Böhler, C.; Nielsen, P. E.; Orgel, L. E. Template Switching Between PNA and RNA Oligonucleotides. Nature 1995, 376, 578-581.
Nielsen, P. E.; Egholm, M.; Berg, R. H.; Buchardt, O. Sequence-Selective Recognition of DNA by Strand Displacement With a Thymine-Substituted Polyamide. Science 1991, 254, 1497-1500.