Lyngbyastatin 4, a dolastatin 13 analogue with elastase and chymotrypsin inhibitory activity from the marine cyanobacterium Lyngbya confervoides.
Lyngbyastatin 4 (1), a new depsipeptide containing the unusual amino acid homotyrosine and a 3-amino-6-hydroxy-2-piperidone (Ahp) residue, was isolated from a collection of the marine cyanobacterium Lyngbya confervoides off the Florida Atlantic coast. Its gross structure was determined by NMR spectroscopy, and the configurations of asymmetric centers were assigned after chiral HPLC analysis of hydrolysis products. Lyngbyastatin 4 (1) is an analogue of the sea hare isolate dolastatin 13 and several marine cyanobacterial metabolites, further supporting the notion that many of the dolastatins are of cyanobacterial origin. Lyngbyastatin 4 (1) selectively inhibits elastase and chymotrypsin in vitro over other serine proteases with IC50 values of 0.03 and 0.30 microM, respectively.
Matthew
Susan
S
Department of Medicinal Chemistry, University of Florida, 1600 SW Archer Road, Gainesville, Florida 32610, USA.
Ross
Cliff
C
Rocca
James R
JR
Paul
Valerie J
VJ
Luesch
Hendrik
H
D000818:Animals; D001267:Atlantic Ocean; D002417:Cattle; D002918:Chymotrypsin / Q000037:antagonists & inhibitors*; D000458:Cyanobacteria / Q000737:chemistry*; D047630:Depsipeptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005431:Florida; D008386:Marine Biology; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry; D010179:Pancreas / Q000201:enzymology; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D011480:Protease Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D013552:Swine
D047630:Depsipeptides; D009842:Oligopeptides; D011480:Protease Inhibitors; C433549:dolastatin 13; C517728:lyngbyastatin 4; D002918:Chymotrypsin; D010196:Pancreatic Elastase