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Abstract :
[en] Pseudodesmine A is a cyclic lipodepsipeptide of nine residues which presents a moderate antibacterial activity and whose structure has been resolved by X-ray and NMR1,2. In acetonitrile, Pseudodesmine A is monomeric while in chloroform it has the same structure but assemble in a supramolecular complex. This structure could associate with membranes and be responsible of the biological activity of this peptide. Comparison of the NMR data between the two solvents has given indications on the intermolecular contacts that arise in chloroform and a model for the self association was proposed2,3. To study in more details this assembly, molecular dynamics have been carried on. In acetonitrile, the peptide show transient interactions while in chlorofom interactions between monomers was always observed. As stated in Sinnaeve et al. in 2009, these interactions arise mainly between the backbone protons of the LEU1 and the GLN2, the GLN2 sidechain and the loop located on the opposite end of the monomer structure. From 10 simulations of dimerization, hydrogen bonds were followed and specific interaction patterns were identified regarding the hydrogen bonds formed. The peptide interactions are mainly described by 13 interaction patterns; 8 with the peptides in a linear configuration, 1 perpendicular and 4 with peptides side by side. The patterns are characterized by 2 to 4 hydrogen bonds. From the linear dimer, it is possible to reconstruct filaments and, by combining a linear and a lateral dimer, it is possible to build fibrils with multi filaments, as expected in the NMR derived model. Besides, the perpendicular dimer can gives peptide rings that can also explain the potential ability of this peptide to form ion pores in membranes.
1. Sinnaeve, D., Michaux, C., Van hemel, J., Vandenkerckhove, J., Peys, E., Borremans, F. a. M., Sas, B., Wouters, J. and Martins, J. C. Tetrahedron 2009, 65, 4173–4181.
2. Sinnaeve, D., Hendrickx, P. M. S., Van Hemel, J., Peys, E., Kieffer, B. and Martins, J. C. Chemistry (Weinheim an der Bergstrasse, Germany) 2009, 15, 12653–62.
3. Sinnaeve, D., Delsuc, M.-A., Martins, J. C. and Kieffer, B. Chemical Science 2012, 3, 1284.
