Impact of a stereocentre inversion in cyclic lipodepsipeptides from the viscosin group: a comparative study of the viscosinamide and pseudodesmin conformation and self-assembly.
The viscosin group covers a series of cyclic lipodepsipeptides (CLPs) produced by Pseudomonas bacteria, with a range of biological functions and antimicrobial activities. Their oligopeptide moieties are composed of both L- and D-amino acids. Remarkably, the Leu5 amino acid-centrally located in the nonapeptide sequence-is the sole residue found to possess either an L or D configuration, depending on the producing strain. The impact of this D/L switch on the solution conformation was investigated by NMR-restrained molecular modelling of the epimers pseudodesmin A and viscosinamide A. Although the backbone fold remained unaffected, the D/L switch adjusted the segregation between hydrophobic and hydrophilic residues, and thus the amphipathicity. It also influenced the self-assembly capacity in organic solvents. Additionally, several new minor variants of viscosinamide A from Pseudomonas fluorescens DR54 were identified, and an NMR assay is proposed to assess the presence of either an L- or D-Leu5.
NMR and Structure Analysis Unit, Department of Organic and Macromolecular Chemistry, Ghent University, Krijgslaan 281 S4, 9000 Ghent (Belgium).
Niels
N
Geudens
Matthias
M
De Vleeschouwer
Krisztina
K
Fehér
Hassan
H
Rokni-Zadeh
Maarten G K
MG
Ghequire
Annemieke
A
Madder
René
R
De Mot
José C
JC
Martins
Davy
D
Sinnaeve
D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010456:Peptides, Cyclic / Q000737:chemistry*; D011551:Pseudomonas fluorescens / Q000737:chemistry*; D013237:Stereoisomerism
D010456:Peptides, Cyclic; C546867:pseudodesmin A; C121478:viscosinamide; C062796:viscosin
conformational analysis; cyclic lipopeptides; natural products; self-assembly; structure-activity relationships