Tiglicamides A-C, cyclodepsipeptides from the marine cyanobacterium Lyngbya confervoides.
The Floridian marine cyanobacterium Lyngbya confervoides afforded cyclodepsipeptides, termed tiglicamides A-C (1-3), along with their previously reported analogues largamides A-C (4-6), all of which possess an unusual tiglic acid moiety. Their structures were deduced by one- and two-dimensional NMR combined with mass spectrometry and the absolute configurations established by chiral HPLC and Marfey's analysis of the degradation products. Compounds 1-3 moderately inhibited porcine pancreatic elastase in vitro with IC(50) values from 2.14 to 7.28 microM. Compounds 1-6 differ from each other by one amino acid residue within the cyclic core structure, suggesting an unusually relaxed substrate specificity of the nonribosomal peptide synthetase that is the putative biosynthetic enzyme responsible for the corresponding amino acid incorporation.
Matthew
Susan
S
Department of Medicinal Chemistry, University of Florida, Gainesville, Florida 32610, USA.
Paul
Valerie J
VJ
Luesch
Hendrik
H
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003437:Crotonates / Q000032:analysis; D000458:Cyanobacteria / Q000737:chemistry*; D047630:Depsipeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology; D045782:Hemiterpenes; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D010453:Peptide Synthases / Q000378:metabolism; D013379:Substrate Specificity; D013552:Swine
D000596:Amino Acids; D003437:Crotonates; D047630:Depsipeptides; D004791:Enzyme Inhibitors; D045782:Hemiterpenes; C548524:tiglicamide A; C548523:tiglicamide B; C548525:tiglicamide C; D010196:Pancreatic Elastase; D010453:Peptide Synthases; C009489:tiglic acid