Effect of peptide lipidation on membrane perturbing activity: a comparative study on two trichogin analogues.
The effect of lipidation on the membrane perturbing activity of peptaibol antibiotics was investigated by performing a comparative study on two synthetic analogues of the natural peptide trichogin GA IV. Both analogues were labeled with a hydrophobic fluorescent probe, but one of them lacked the N-terminal n-octanoyl chain, present in the natural peptide. Spectroscopic studies show that the fatty acyl chain produces two opposite effects: it increases the affinity of the monomeric peptide for the membrane phase, but, at the same time, it favors peptide aggregation in water, thus inhibiting membrane binding by reducing the effective monomer concentration. In the membrane phase the two analogues exhibit the same aggregation and orientation behavior, indicating that the n-octanoyl chain plays no specific role in determining their orientation or membrane perturbing activity. Indeed, the dependence of peptide-induced membrane leakage on total peptide concentration is basically the same for the two analogues, because the aforementioned opposite effects, caused by peptide lipidation, tend to balance. These findings make questionable the use of lipidation as a general method for increasing the peptide membrane-perturbing activity, as its validity seems to be restricted to parent compounds of limited overall hydrophobicity.
Gatto
Emanuela
E
Dipartimento di Scienze e Tecnologie Chimiche, Università di Roma Tor Vergata, 00133 Roma, Italy.
Mazzuca
Claudia
C
Stella
Lorenzo
L
Venanzi
Mariano
M
Toniolo
Claudio
C
Pispisa
Basilio
B
D020003:1-Octanol / Q000737:chemistry; D000595:Amino Acid Sequence; D001665:Binding Sites; D002463:Cell Membrane Permeability; D005456:Fluorescent Dyes / Q000737:chemistry*; D006020:Glycopeptides / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D055666:Lipopeptides; D008560:Membrane Fluidity; D008563:Membrane Lipids / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D013997:Time Factors
D005456:Fluorescent Dyes; D006020:Glycopeptides; D055666:Lipopeptides; D008563:Membrane Lipids; D008565:Membrane Proteins; D010455:Peptides; C116419:trichogin GA IV; D020003:1-Octanol