title: Advancing cell wall inhibitors towards clinical applications.
abstract: Natural products represent a major source of approved drugs and still play an important role in supplying chemical diversity. Consistently, 2014 has seen new, natural product-derived antibiotics approved for human use by the US Food and Drug Administration. One of the recently approved second-generation glycopeptides is dalbavancin, a semi-synthetic derivative of the natural product A40,926. This compound inhibits bacterial growth by binding to lipid intermediate II (Lipid II), a key intermediate in peptidoglycan biosynthesis. Like other recently approved antibiotics, dalbavancin has a complex history of preclinical and clinical development, with several companies contributing to different steps in different years. While our work on dalbavancin development stopped at the previous company, intriguingly our current pipeline includes two more Lipid II-binding natural products or derivatives thereof. In particular, we will focus on the properties of NAI-107 and related lantibiotics, which originated from recent screening and characterization efforts.
authors.affiliation: KtedoGen Srl, Viale Ortles 22/4, 20139, Milan, Italy.|Naicons Srl, Viale Ortles 22/4, 20139, Milan, Italy.
authors.forename: Sonia I
authors.initials: SI
authors.lastname: Maffioli
authors.affiliation: KtedoGen Srl, Viale Ortles 22/4, 20139, Milan, Italy.
authors.forename: João C S
authors.initials: JC
authors.lastname: Cruz
authors.affiliation: KtedoGen Srl, Viale Ortles 22/4, 20139, Milan, Italy.|Naicons Srl, Viale Ortles 22/4, 20139, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Monciardini
authors.affiliation: KtedoGen Srl, Viale Ortles 22/4, 20139, Milan, Italy.|Naicons Srl, Viale Ortles 22/4, 20139, Milan, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Sosio
authors.affiliation: KtedoGen Srl, Viale Ortles 22/4, 20139, Milan, Italy. sdonadio@naicons.com.|Naicons Srl, Viale Ortles 22/4, 20139, Milan, Italy. sdonadio@naicons.com.
authors.forename: Stefano
authors.initials: S
authors.lastname: Donadio
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D001430:Bacteriocins / Q000378:metabolism / Q000494:pharmacology; D001688:Biological Products / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D002473:Cell Wall / Q000187:drug effects*; D017277:Drug Approval; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008969:Molecular Sequence Data; D017334:Teicoplanin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D014481:United States; D014486:United States Food and Drug Administration; D014538:Uridine Diphosphate N-Acetylmuramic Acid / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D001688:Biological Products; D014538:Uridine Diphosphate N-Acetylmuramic Acid; C528150:microbisporicin; C069249:muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol; D017334:Teicoplanin; C469289:dalbavancin