title: Structure, stereochemistry, and biological activity of integramycin, a novel hexacyclic natural product produced by Actinoplanes sp. that inhibits HIV-1 integrase.
abstract: [structure: see text] HIV-1 integrase is a critical enzyme for viral replication, and its inhibition is an emerging target for potential antiviral chemotherapy. We have discovered a novel inhibitor, integramycin, from screening of fermentation extracts using an in vitro assay. Integramycin possesses a hexacyclic ring system and exhibited an IC50 value of 4 microM against HIV-1 integrase (strand transfer). The isolation, structure elucidation, stereochemistry, conformation, and biological activity has been described.
authors.affiliation: Merck Research Laboratories, Rahway, New Jersey 07065, USA. sheo_singh@merck.com
authors.forename: Sheo B
authors.initials: SB
authors.lastname: Singh
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Zink
authors.forename: Brian
authors.initials: B
authors.lastname: Heimbach
authors.forename: Olga
authors.initials: O
authors.lastname: Genilloud
authors.forename: Ana
authors.initials: A
authors.lastname: Teran
authors.forename: Keith C
authors.initials: KC
authors.lastname: Silverman
authors.forename: Russell B
authors.initials: RB
authors.lastname: Lingham
authors.forename: Peter
authors.initials: P
authors.lastname: Felock
authors.forename: Daria J
authors.initials: DJ
authors.lastname: Hazuda
mesh_terms: D005285:Fermentation; D019428:HIV Integrase Inhibitors / Q000737:chemistry*; D015497:HIV-1; D009682:Magnetic Resonance Spectroscopy; D008848:Micromonosporaceae / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D009281:Naphthalenes / Q000737:chemistry* / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D013141:Spiro Compounds / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D019428:HIV Integrase Inhibitors; D009281:Naphthalenes; D013141:Spiro Compounds; C489772:integramycin