A glycosylated, labionin-containing lanthipeptide with marked antinociceptive activity

Marianna Iorio, Oscar Sasso, Sonia I. Maffioli, Rosalia Bertorelli, Paolo Monciardini, Margherita Sosio, Fabiola Bonezzi, Maria Summa, Cristina Brunati, Roberta Bordoni, Giorgio Corti, Glauco Tarozzo, Daniele Piomelli, Angelo Reggiani, Stefano Donadio

Research output: Contribution to journalArticle

Abstract

Among the growing family of ribosomally synthesized, post-translationally modified peptides, particularly intriguing are class III lanthipeptides containing the triamino acid labionin. In the course of a screening program aimed at finding bacterial cell wall inhibitors, we discovered a new lanthipeptide produced by an Actinoplanes sp. The molecule, designated NAI-112, consists of 22 amino acids and contains an N-terminal labionin and a C-terminal methyl-labionin. Unique among lanthipeptides, it carries a 6-deoxyhexose moiety N-linked to a tryptophan residue. Consistently, the corresponding gene cluster encodes, in addition to the LanKC enzyme characteristic of this lanthipeptide class, a glycosyl transferase. Despite possessing weak antibacterial activity, NAI-112 is effective in experimental models of nociceptive pain, reducing pain symptoms in mice in both the formalin and the chronic constriction injury tests. Thus, NAI-112 represents, after the labyrinthopeptins, the second example of a lanthipeptide effective against nociceptive pain.

Original languageEnglish
Pages (from-to)398-404
Number of pages7
JournalACS Chemical Biology
Volume9
Issue number2
DOIs
Publication statusPublished - Feb 21 2014

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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    Iorio, M., Sasso, O., Maffioli, S. I., Bertorelli, R., Monciardini, P., Sosio, M., Bonezzi, F., Summa, M., Brunati, C., Bordoni, R., Corti, G., Tarozzo, G., Piomelli, D., Reggiani, A., & Donadio, S. (2014). A glycosylated, labionin-containing lanthipeptide with marked antinociceptive activity. ACS Chemical Biology, 9(2), 398-404. https://doi.org/10.1021/cb400692w