Lipopeptaibols, a novel family of membrane active, antimicrobial peptides

Abstract

Lipopeptaibols are members of a novel group of naturally occurring, short peptides with antimicrobial activity, characterized by a lipophilic acyl chain at the N-terminus, a high content of the turn/helix forming alpha-aminoisobutyric acid and a 1,2-amino alcohol at the C-terminus. The amino acid sequences range from 6 to 10 residues and the fatty acyl moieties from 8 to 15 carbon atoms. The peptide portion of lipopeptaibols can be shorter than those of the nonlipidated peptaibols that range from 10 to 19 amino acid residues. The longest peptides fold into a mixed 3(10)/alpha helix, whereas the shortest peptides tend to adopt a beta-turn/sheet structure. Using solution methodologies, a series of analogues of trichogin GA IV was synthesized which allowed determination of the minimal lipid chain and peptide main-chain lengths for the onset of membrane activity and exploitation of a number of spectroscopic techniques aimed at determining its preferred conformation under a variety of conditions and investigating in detail its mode of interaction with, and its effect on, the phospholipid membranes.

The occurrence of peptaibols and structurally related peptaibiotics in fungi and their mass spectrometric identification via diagnostic fragment ions

“…An excellent review, summarizing related sub-families of peptaibols, has recently been presented by Chugh and Wallace [23]. Lipopeptaibol antibiotics were reviewed by Toniolo et al [24]; and detailed information on mass spectrometry of leucinostatin antibiotics was given by Isogai et al [25]. Due to the still growing number of peptaibiotics, recurrent isolations may occur frequently.…”

Peptaibiomics: Towards a Myriad of Bioactive Peptides Containing Cα‐Dialkylamino Acids?

“…The majority of Aib-containing peptides carries a C-terminal residue representing a 2-amino alcohol, and this subgroup is, therefore, referred to as peptaibols [2] [3]. In strongly lipophilic peptaibols, the N-terminus is acylated by octanoic, decanoic, or cis-dec-4-enoic acid, and these are named lipopeptaibols [4]. In the third subfamily of lipoaminopeptides (also named aminolipopeptides), the Nterminus is substituted by unbranched, a-or g-methyl-branched, saturated or unsaturated C 4 -C 15 fatty acids.…”

Enhanced Patch-Clamp Technique to Study Antimicrobial Peptides and Viroporins, Inserted in a Cell Plasma Membrane with Fully Inactivated Endogenous Conductances

“…The former peptide is the major component of the neutral fraction of the peptaibol antibiotic alamethicin. The peptaibols (Toniolo et al, 2001) are members of a group of naturally occurring short peptides produced by fungi of the genus Trichoderma, characterized by an N-terminal acyl group, a C-terminal 1,2-aminoalcohol and a high content of the non-proteinogenic C α -tetrasubstituted α-amino acid Aib (α-aminoisobutyric acid). Key amino acids of the F50/5 peptide sequence were also modified to understand their implication on the biophysical characteristics of the pore www.intechopen.com .…”