title: Mutremdamide A and koshikamides C-H, peptide inhibitors of HIV-1 entry from different Theonella species.
abstract: A new sulfated cyclic depsipeptide, termed mutremdamide A, and six new highly N-methylated peptides, termed koshikamides C-H, were isolated from different deep-water specimens of Theonella swinhoei and Theonella cupola. Their structures were determined using extensive 2D NMR, ESI, or CDESI and QTOF-MS/MS experiments and absolute configurations established by quantum mechanical calculations, advanced Marfey's method, and chiral HPLC. Mutremdamide A displays a rare 2-amino-3-(2-hydroxyphenyl)propanoic acid and a new N(delta)-carbamoyl-beta-sulfated asparagine. Koshikamides C-E are linear undecapeptides, and koshikamides F-H are 17-residue depsipeptides containing a 10-residue macrolactone. Koshikamides F and G differ from B and H in part by the presence of the conjugated unit 2-(3-amino-5-oxopyrrolidin-2-ylidene)propanoic acid. Cyclic koshikamides F and H inhibited HIV-1 entry at low micromolar concentrations while their linear counterparts were inactive. The Theonella collections studied here are distinguished by co-occurrence of mutremdamide A, koshikamides, and theonellamides, the combination of which appears to define a new Theonella chemotype that can be found in deeper waters.
authors.affiliation: Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Alberto
authors.initials: A
authors.lastname: Plaza
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bifulco
authors.forename: Milena
authors.initials: M
authors.lastname: Masullo
authors.forename: John R
authors.initials: JR
authors.lastname: Lloyd
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Keffer
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Colin
authors.forename: John N A
authors.initials: JN
authors.lastname: Hooper
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Bell
authors.forename: Carole A
authors.initials: CA
authors.lastname: Bewley
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D047630:Depsipeptides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008387:Marine Toxins / Q000737:chemistry*; D008968:Molecular Conformation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D047232:Theonella / Q000737:chemistry*
chemical_list: D047630:Depsipeptides; D008387:Marine Toxins; D010456:Peptides, Cyclic; C553195:koshikamide F; C553188:mutremdamide A
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