Molassamide, a depsipeptide serine protease inhibitor from the marine cyanobacterium Dichothrix utahensis.
A new dolastatin 13 analogue, molassamide (1), was isolated from cyanobacterial assemblages of Dichothrix utahensis collected from the Molasses Reef, Key Largo, Florida, and from Brewer's Bay, St. Thomas, U.S. Virgin Islands. This is the first peptide reported from the cyanobacterial genus Dichothrix and the first natural product isolated from marine Dichothrix spp. Its planar structure was determined by NMR spectroscopic techniques, and the configurations of the asymmetric centers were assigned after chiral HPLC analysis of the hydrolysis products. The depsipeptide 1 exhibited protease-inhibitory activity, with IC(50) values of 0.032 and 0.234 muM against elastase and chymotrypsin, respectively. There was no apparent inhibition of trypsin at 10 microM, the highest concentration tested.
Gunasekera
Sarath P
SP
Smithsonian Marine Station at Ft. Pierce, Ft. Pierce, Florida 34949, USA.
Miller
Margaret W
MW
Kwan
Jason C
JC
Luesch
Hendrik
H
Paul
Valerie J
VJ
D000818:Animals; D000458:Cyanobacteria / Q000737:chemistry; D047630:Depsipeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008386:Marine Biology; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry; D010179:Pancreas / Q000201:enzymology; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D013552:Swine
D047630:Depsipeptides; D009842:Oligopeptides; D015842:Serine Proteinase Inhibitors; C433549:dolastatin 13; C548939:molassamide; D010196:Pancreatic Elastase