antimicrobial agents; dendrimers; biofilms; gene and siRNA delivery; peptides
Siriwardena Thissa N., Stach Michaela, He Runze, Gan Bee Ha, Javor Sacha, Heitz Marc, Ma Lan, Cai Xiangjun, Chen Peng, Wei Dengwen, Li Hongtao, Ma Jun, Koehler Thilo, van Delden Christian, Darbre Tamis, Reymond Jean-Louis (2017), Lipidated Peptide Dendrimers Killing Multidrug-Resistant Bacteria, in
JACS, Journal of the American Chemical Society, 140(1), 423-432.
He Runze, Di Bonaventura Ivan, Visini Ricardo, Gan Bee Ha, Fu Yongchun, Probst Daniel, Lüscher Alexandre, Köhler Thilo, van Delden Christian, Stocker Achim, Hong Wenjing, Darbre Tamis, Reymond Jean-Louis (2017), Design, crystal structure and atomic force microscopy study of thioether ligated D,L-cyclic antimicrobial peptides against multidrug resistant Pseudomonas aeruginosa, in
Chemical Science, 8, 7464-7475.
Di Bonaventura Ivan, Jin Xian, Visini Ricardo, Probst Daniel, Javor Sacha, Gan Bee Ha, Michaud Gaëlle, Natalello Antonio, Doglia Silvia Maria, Köhler Thilo, van Delden Christian, Stocker Achim, Darbre Tamis, Reymond Jean-Louis (2017), Chemical space guided discovery of antimicrobial bridged bicyclic peptides against Pseudomonas aeruginosa and its biofilms, in
Chemical Science, 8(10), 6784-6798.
Kwok A., Eggimann G. A., Heitz M., Reymond Jean-Louis, Hollfelder F., Darbre T. (2016), Efficient Transfection of siRNA by Peptide Dendrimer–Lipid Conjugates, in
ChemBioChem Communications, 17, 2223-2229.
Abdel-Sayed P., Kaeppli A., Siriwardena T., Darbre T., Perron K., Jafari P., Reymond J.-L., Pioletti D. P., Applegate L. A. (2016), Anti-Microbial Dendrimers against Multidrug-Resistant P. aeruginosa Enhance the Angiogenic Effect of Biological Burn-wound Bandages, in
Nature: Scientific Reports, 6, 1-10.
Roethlisberger P, Istrate A., Marcaida Lopez M. J., Visini R., Stocker A., Reymond J.-L., Leumann C. J. (2016), X-ray structure of a lectin-bound DNA duplex containing an unnatural phenanthrenyl pair, in
Chemical Communications, 52(26), 4749-4752.
Michaud Gaëlle, Visini Ricardo, Bergmann Myriam, Salerno Gianluca, Bosco Rosa, Gillon Emilie, Richichi Barbara, qNativi Cristina, Imberty Anne, Stocker Achim, Darbre Tamis, Reymond Jean-Louis (2015), Overcoming antibiotic resistance in Pseudomonas aeruginosa biofilms using glycopeptide dendrimers, in
Chemical Science, 7, 166-182.
Jin Xian, Awale Mahendra, Zasso Michaël, Kostro DAniel, Patiny Luc, Reymond J.-L. (2015), PDB-Explorer: a web-based interactive map of the protein data bank in shape space, in
BMC Bioinformatics, 16(339), 1-15.
PIres João, Siriwardena Thissa N., Stach Michaela, Tinguely Regula, Kasraian Sara, Luzzaro Francesco, Leib Stephen L., Darbre Tamis, Reymond Jean-Louis, Endimiani Andrea (2015), In Vitro Activity of the Novel Antimicrobial Peptide Dendrimer G3KL against Multidrug-Resistant Acinetobacter baumannii and Pseudomonas aeruginosa, in
Antimicrobial Agents and Chemotherapy, 59(12), 7915-7918.
Bergmann Myriam, Michaud Gaëlle, Visini Ricardo, Jin Xian, Gillon Emilie, Stocker Achim, Imbertry Anne, Darbre Tamis, Reymond Jean-Louis (2015), Multivalency effects on Pseudomonas aeruginosa biofilm inhibition and dispersal by glycopeptide dendrimers targeting lectin LecA, in
Organic & Biomolecular Chemistry, 14, 138-142.
Visini Ricardo, Jin Xian, Bergmann Myriam, Michaud Gaëlle, Pertici Francesca, Fu Ou, Pukin Aliaksei, Branson Thomas R., Thies-Weesie Dominique M. E., Kemmink Johan, Gillon Emilie, Imberty Anne, Stocker Achim, Darbre Tamis, Pieters Roland J., Reymond Jean-Louis (2015), Structural Insight into Multivalent Galactoside Binding to Pseudomonas aeruginosa Lectin LecA, in
ACS Chemical Biology, 10, 2455-2462.
Bartoloni Marco, Jin Xian, Marcaida Marie José, Banha João, Dibonaventura Ivan, Bongoni Swathi, Bartho Kathrin, Gräbner Olivia, Sefkow Michael, Darbre Tamis, Reymond Jean-Louis (2015), Bridged bicyclic peptides as potential drug scaffolds: synthesis, structure, protein binding and stability, in
Chemical Science, 6, 5473-5490.
The “Chemical space” describes the ensemble of all possible chemical compounds, in particular those of interest as drugs for medical use, spanning from small organic molecules such as aspirin to large proteins such as antibodies. The concept of chemical space calls for considering every possible molecule beyond those already known. In this proposal we focus on peptides, an important class of intermediate size molecules found mostly as linear of cyclic chains of up to 50 amino acids. When reflecting on design possibilities, an entire world of new possibilities opens when using diamino acids or amino diacids as branching points in the peptide chain, revealing topologies not found in nature such as multi-branched peptide dendrimers and polycyclic peptides. Unlike linear or monocyclic peptides, these branched peptides are resistant to serum degradation and display remarkable biological properties by multivalency effects (peptide dendrimers) and conformational rigidity (polycyclic peptides). The proposal unfolds in four specific projects to explore the properties of this promising new class of bioactive molecules: computer-aided peptide design, antimicrobials and DNA/si-RNA transfection, biofilm inhibitors, and bridged bicyclic peptides.