Spectroscopically labeled peptaibiotic analogs: the 4‐nitrophenylalanine infrared absorption probe inserted at different positions into trichogin GA IV

Abstract

A set of three analogs of the 10-residue, membrane-active lipopeptaibiotic trichogin GA IV, labeled with the promising 4-nitrophenylalanine IR absorption probe for local polarity, was synthesized by the solid-phase methodology, chromatographically purified, and extensively characterized. A single residue modification was inserted near the N-terminus, in the central region, or at the C-terminus. A solution conformational analysis, carried out by FT-IR absorption, CD, and 2D-NMR combined with molecular dynamics calculations, indicates that the mono-labeled analogs maintain the overall helical properties of the parent compound. Membrane permeabilization measurements and antimicrobial tests revealed that they possess membrane-modifying properties and in vitro antibacterial activities analogous to those of the natural lipopeptaibiotic. Our IR absorption and attenuated total reflectance investigations in various environments, from which water was excluded for solubility reasons, showed that the 1350 cm(-1) 4-nitrobenzyl band is a reporter group of rather limited sensitivity.

Insights into peptide‐membrane interactions of newly synthesized, nitroxide‐containing analogs of the peptaibiotic trichogin GAIV using EPR

“…Its primary structure is Oct‐Aib‐Gly‐Leu‐Aib‐Gly‐Gly‐Leu‐Aib‐Gly‐Ile‐Lol (Oct is 1‐octanoyl, Lol is the 1,2‐amino alcohol leucinol). To unravel the mechanism of action of TG and to possibly develop a drug from TG, in the last two decades we have been synthesizing selected TG analogs and investigating them by means of a variety of physicochemical techniques . The presence of the three helix‐inducing Aib residues allows TG to adopt a helical structure in the crystal state, in organic solvents, in membranes, and in membrane mimetic environments .…”

Cotton functionalized with peptides: characterization and synthetic methods

“…There is a great demand for durable antimicrobial textiles based on nontoxic bioactive compounds. To contribute to this topic, we started a research program that heavily relies on our expertise in the field of antibacterial peptides . The main advantage of using amino acids and peptides comes from their presence in nature.…”

Conformational properties, membrane interaction, and antibacterial activity of the peptaibiotic chalciporin A: Multitechnique spectroscopic and biophysical investigations on the natural compound and labeled analogs

“…Peptaibiotics are constituents of a family of naturally occurring, linear peptides , 4‐ to 21‐amino acid residue long, with membrane and antibiotic activities, characterized by a very high percentage of the effective helix‐supporting, C α ‐tetrasubstituted Aib (α‐aminoisobutyric acid) residue . Their well‐known, relevant peculiarity for drug development (peptide bond stability in the presence of plasma enzymes) is strictly related to the multiple presence of this sterically highly hindered, quaternary amino acid in the primary structure.…”