Lobocyclamides A-C, lipopeptides from a cryptic cyanobacterial mat containing Lyngbya confervoides.
The structures of lipopeptides lobocyclamides A (1), B (2), and C (3) were solved using a combination of mass spectrometry, 2D NMR spectroscopy, and degradative analysis. Lobocyclamides B and C are the first peptides reported with the unusual amino acid 4-hydroxythreonine and also incorporate the rare homologous long-chain beta-amino acids 3-aminooctanoic acid and 3-aminodecanoic acid, respectively. The absolute configurations of the amino acid residues in each compound were assigned, after acid hydrolysis, by either direct chiral HPLC comparison with authentic standards or by prior derivatization by Marfey's method and reversed-phase HPLC. Both compounds exhibited moderate antifungal activity against a panel of Candida spp., including two fluconazole-resistant strains. When tested as a mixture, lobocyclamides A and B displayed synergistic in vitro antifungal activity, a phenomenon noted earlier for the related peptides laxaphycins A and B.
MacMillan
John B
JB
Department of Chemistry, One Shields Avenue, University of California, Davis, California 95616, USA.
Ernst-Russell
Michael A
MA
de Ropp
Jeffrey S
JS
Molinski
Tadeusz F
TF
D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology; D002175:Candida / Q000187:drug effects; D000458:Cyanobacteria / Q000737:chemistry*; D004351:Drug Resistance; D015725:Fluconazole; D006868:Hydrolysis; D008074:Lipoproteins / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology
D000935:Antifungal Agents; D008074:Lipoproteins; D010456:Peptides, Cyclic; C475800:lobocyclamide A; C458300:lobocyclamide B; C475801:lobocyclamide C; D015725:Fluconazole