A Temperature-Driven, Reversible, Helical-Handedness Inversion in Peptaibol Analogues Tuned by the C-Terminal Capping Moiety

Marta De Zotti, Victoria N. Syryamina, Rohanah Hussain, Edoardo Longo, Giuliano Siligardi, Sergei A. Dzuba, Lorenzo Stella, Fernando Formaggio

Research output: Contribution to journalArticlepeer-review

Abstract

Trichogin is a natural peptide endowed with antimicrobial and antitumor activity. A member of the peptaibol family, trichogin possesses a C-terminal amino alcohol. In the past, this moiety was substituted for a methyl ester for synthetic purposes and it was observed that this apparently slight modification caused significant changes in the peptide bioactivity. With the aim of understanding the reasons behind such observations, a detailed spectroscopic study on a number of trichogin analogues has been performed. Herein, data obtained from synchrotron radiation circular dichroism, NMR spectroscopy, and fluorescence spectroscopy in organic solvents at cryogenic temperatures are compared with those independently acquired by means of EPR spectroscopy at 80 K. It is unambiguously revealed that the presence of a reversible, temperature-driven, screw-sense interconversion from a right- to left-handed helix is determined by the C-terminal capping moiety. Data demonstrate, for the first time, the key role of a C-terminal methyl ester in promoting peptide screw-sense inversion.

Original languageEnglish
Pages (from-to)2125-2132
Number of pages8
JournalChemBioChem
Volume20
Issue number16
DOIs
Publication statusPublished - 16 Aug 2019

Keywords

  • antimicrobial peptides
  • conformational analysis
  • helical structures
  • screw-sense switching
  • synchrotron radiation circular dichroism
  • SCREW-SENSE
  • LIPOPEPTAIBOL
  • ANTIBACTERIAL
  • MEMBRANE INTERACTION
  • ACHIRAL PEPTIDE
  • RESONANCE
  • TRICHOGIN GA IV
  • ALPHA-AMINO-ACID
  • CONFORMATIONAL-ANALYSIS
  • PREFERENCE

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