Solution conformational analysis of amphiphilic helical, synthetic analogs of the lipopeptaibol trichogin GA IV.
The step-by-step synthesis by solution methods of the [Ser2,5,6,9, Leu-OMe11] analog of trichogin GA IV is described. The four Ser residues have been incorporated into the sequence as replacements of the naturally occurring Gly residues to increase the amphiphilicity of the 3D-structure of the lipopeptaibol. A detailed solution conformational analysis has been performed on this undecapeptide and its prototypical [Leu-OMe11] trichogin GA IV analog using FTIR absorption and CD spectroscopies, and two-dimensional NMR under a variety of experimental conditions, including a membrane-mimetic environment. Both peptides adopt a mixed 3(10)/alpha-helical structure, which in the micellar system was found to be less flexible for the Ser-containing analog. For both analogs permeability measurements revealed membrane-modifying properties comparable to those of the natural lipopeptaibol.
Monaco
V
V
Biopolymer Research Center, CNR, Department of Organic Chemistry, University of Padova, Italy.
Locardi
E
E
Formaggio
F
F
Crisma
M
M
Mammi
S
S
Peggion
E
E
Toniolo
C
C
Rebuffat
S
S
Bodo
B
B
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D002942:Circular Dichroism; D006020:Glycopeptides; D055666:Lipopeptides; D009682:Magnetic Resonance Spectroscopy; D010455:Peptides; D011487:Protein Conformation; D017510:Protein Folding
D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D055666:Lipopeptides; D010455:Peptides; C116419:trichogin GA IV