title: A glycosylated, labionin-containing lanthipeptide with marked antinociceptive activity.
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.affiliation: NAICONS Srl , Via Fantoli 16/15, 20138 Milano, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Iorio
authors.forename: Oscar
authors.initials: O
authors.lastname: Sasso
authors.forename: Sonia I
authors.initials: SI
authors.lastname: Maffioli
authors.forename: Rosalia
authors.initials: R
authors.lastname: Bertorelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Monciardini
authors.forename: Margherita
authors.initials: M
authors.lastname: Sosio
authors.forename: Fabiola
authors.initials: F
authors.lastname: Bonezzi
authors.forename: Maria
authors.initials: M
authors.lastname: Summa
authors.forename: Cristina
authors.initials: C
authors.lastname: Brunati
authors.forename: Roberta
authors.initials: R
authors.lastname: Bordoni
authors.forename: Giorgio
authors.initials: G
authors.lastname: Corti
authors.forename: Glauco
authors.initials: G
authors.lastname: Tarozzo
authors.forename: Daniele
authors.initials: D
authors.lastname: Piomelli
authors.forename: Angelo
authors.initials: A
authors.lastname: Reggiani
authors.forename: Stefano
authors.initials: S
authors.lastname: Donadio
mesh_terms: D000595:Amino Acid Sequence; D000700:Analgesics / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D001430:Bacteriocins / Q000737:chemistry* / Q000235:genetics / Q000627:therapeutic use; D005798:Genes, Bacterial; D006031:Glycosylation; D008297:Male; D051379:Mice; D008848:Micromonosporaceae / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family; D010146:Pain / Q000188:drug therapy; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000627:therapeutic use
chemical_list: D000700:Analgesics; D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D010455:Peptides