Largamides A-H, unusual cyclic peptides from the marine cyanobacterium Oscillatoria sp.
Seven new depsipeptides, termed largamides A-G (1-7), and one new cyclic peptide, largamide H (8), have been isolated from the marine cyanobacterium Oscillatoria sp. Their structures were determined by NMR and ESI-MS techniques. The absolute configurations were assigned using LC-MS, chiral HPLC, and combined analysis of homonuclear and heteronuclear (2,3)J couplings, along with ROE data. Largamides, isolated from a single homogeneous cyanobacterial collection, represent three different structural classes of peptides. Largamides A-C (1-3) are characterized by the unusual occurrence of a senecioic acid unit, while largamides B (2) and C (3) possess in addition the rare 2-amino-5-(4'-hydroxyphenyl)pentanoic acid (Ahppa) and the novel 2-amino-6-(4'-hydroxyphenyl)hexanoic acid (Ahpha), respectively. Largamides D-G (4-7) are the first 3-amino-6-hydroxy-2-piperidone acid (Ahp)-containing depsipeptides reported with the rare Ahppa unit. Largamide H (8) is a unique cyclic peptide displaying a new 2,5-dihydroxylated beta-amino acid moiety, a methoxylated derivative of Ahppa, and two residues of the nonstandard 2,3-dehydro-2-aminobutanoic acid (Dab). Largamides D-G (4-7) inhibited chymotrypsin with IC(50) values ranging between 4 and 25 microM.
Plaza
Alberto
A
Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0820, USA.
Bewley
Carole A
CA
D002851:Chromatography, High Pressure Liquid; D002918:Chymotrypsin / Q000037:antagonists & inhibitors; D000458:Cyanobacteria / Q000737:chemistry*; D047630:Depsipeptides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D011487:Protein Conformation; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D014871:Water Microbiology
D047630:Depsipeptides; D010456:Peptides, Cyclic; D015842:Serine Proteinase Inhibitors; D002918:Chymotrypsin