Effect of Peptide Lipidation on Membrane Perturbing Activity: A Comparative Study on Two Trichogin Analogues

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• 作者：Emanuela Gatto ; Claudia Mazzuca ; Lorenzo Stella ; Mariano Venanzi ; Claudio Toniolo ; Basilio Pispisa
• 刊名：Journal of Physical Chemistry B
• 出版年：2006
• 出版时间：November 16, 2006
• 年：2006
• 卷：110
• 期：45
• 页码：22813 - 22818
• 全文大小：93K
• 年卷期：v.110,no.45(November 16, 2006)
• ISSN：1520-5207

文摘

The effect of lipidation on the membrane perturbing activity of peptaibol antibiotics was investigated byperforming a comparative study on two synthetic analogues of the natural peptide trichogin GA IV. Bothanalogues were labeled with a hydrophobic fluorescent probe, but one of them lacked the N-terminal n-octanoylchain, present in the natural peptide. Spectroscopic studies show that the fatty acyl chain produces two oppositeeffects: it increases the affinity of the monomeric peptide for the membrane phase, but, at the same time, itfavors peptide aggregation in water, thus inhibiting membrane binding by reducing the effective monomerconcentration. 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 membraneperturbing activity. Indeed, the dependence of peptide-induced membrane leakage on total peptide concentrationis basically the same for the two analogues, because the aforementioned opposite effects, caused by peptidelipidation, tend to balance. These findings make questionable the use of lipidation as a general method forincreasing the peptide membrane-perturbing activity, as its validity seems to be restricted to parent compoundsof limited overall hydrophobicity.