Molassamide, a Depsipeptide Serine Protease Inhibitor from the Marine Cyanobacterium Dichothrix utahensis

Abstract

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 IC50 values of 0.032 and 0.234 µM against elastase and chymotrypsin, respectively. There was no apparent inhibition of trypsin at 10 µM, the highest concentration tested.