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A Temperature‐Driven, Reversible, Helical‐Handedness Inversion in Peptaibol Analogues Tuned by the C‐Terminal Capping Moiety
Author(s) -
De Zotti Marta,
Syryamina Victoria N.,
Hussain Rohanah,
Longo Edoardo,
Siligardi Giuliano,
Dzuba Sergei A.,
Stella Lorenzo,
Formaggio Fernando
Publication year - 2019
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201900235
Subject(s) - moiety , circular dichroism , chemistry , peptide , stereochemistry , nuclear magnetic resonance spectroscopy , linker , crystallography , combinatorial chemistry , biochemistry , computer science , operating system
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.