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.
|
Authors | 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 |
Journal | ACS chemical biology
(ACS Chem Biol)
Vol. 9
Issue 2
Pg. 398-404
(Feb 21 2014)
ISSN: 1554-8937 [Electronic] United States |
PMID | 24191663
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Analgesics
- Anti-Bacterial Agents
- Bacteriocins
- Peptides
|
Topics |
- Amino Acid Sequence
- Analgesics
(chemistry, metabolism, therapeutic use)
- Animals
- Anti-Bacterial Agents
(chemistry, metabolism, therapeutic use)
- Bacteriocins
(chemistry, genetics, therapeutic use)
- Genes, Bacterial
- Glycosylation
- Male
- Mice
- Micromonosporaceae
(chemistry, genetics)
- Molecular Sequence Data
- Multigene Family
- Pain
(drug therapy)
- Peptides
(chemistry, genetics, therapeutic use)
|