Download Bacillus anthracis

Innovative oligourea foldamers with antimicrobial effects:
application to Bacillus anthracis infection.
Stéphanie Antunes1, Céline Douat1, Jean-Philippe Corre2, Pierre Goossens2 and
Gilles Guichard*1
1
University of Bordeaux – CNRS UMR5248, IECB European Institute of Chemistry and Biology, CBMN,
2
2 rue Robert Escarpit, Pessac, France; Laboratories of Pathogenesis of Bacterial Toxi-Infections,
Pasteur Institute, Paris, France.
The increasing antibiotic resistance among pathogens and the emergence of
biological weapons have highlighted the urgent need of new antimicrobial agents. In
this context, the design of unnatural oligomers with predictable folding patterns (i.e.
foldamers) capable of mimicking the amphiphilic character and conformation of natural
antimicrobial peptides, key effector molecules of innate immunity, offers new prospects
[1].
Our group is developing peptidomimetic oligomers incorporating ethylene
diamine units linked by urea bond ((NH-CH(R)-CH2-NH-CO)n, Figure 1a). These
aliphatic oligomers display a strong propensity for helix formation in solution and in the
solid state. More particularly, it has been shown that short chain oligoureas (8-mers)
display a significant activity in vitro against both Gram-negative and positive bacteria
and show some selectivity for bacterial versus eukaryotic cells (eg. OL1, Figure 1b)
[2].
Fig 1. a) N, N’-linked oligourea b) Sequence of the oligourea OL1 designed to adopt a helical amphipathic structure.
We have investigated the activities of such foldamers on capsulated and noncapsulated pathogenic bacterium Bacillus anthracis. Early results on structure-activity
relationship studies carried out by performing series of modifications on a lead
compound (i.e. side-chain replacement, size and backbone modifications) but also
therapeutic activities in vivo in animal models will be reported.
[1]
[2]
G. Guichard, I. Huc (2011), Chem. comm. 47, 5933-5941.
a) P. Claudon, A. Violette, K. Lamour, M. Decossas, S. Fournel, B. Heurtault, J. Godet, Y. Mély,
B. Jamart-Grégoire, M.-C. Averlant-Petit, J.-P. Briand, G. Duportail, H. Monteil, G. Guichard
(2010), Angew. Chem. Int. Ed., 49, 333-336; b) A. Violette, S. Fournel, K. Lamour, O. Chaloin,
B. Frisch, J.-P. Briand, H. Monteil, G. Guichard (2006), Chem. Biol. 13, 531-538.