Abstract
Eight new cyanopeptolins (insulapeptolides A-H) were obtained from the cyanobacterium Nostoc insulare. Their isolation was guided by their bioactivity toward the target enzyme human leukocyte elastase, molecular biological investigations, and MALDI-TOF analysis. These peptides are selective inhibitors of human leukocyte elastase with activities in the nanomolar range. Insulapeptolide D was the most potent compound with an IC(50) value of 85 nM (K(i) value of 36 nM).
MeSH terms
-
Amino Acid Sequence
-
Biological Assay
-
Cathepsin G
-
Cathepsins / antagonists & inhibitors
-
Cathepsins / metabolism
-
Drug Discovery
-
Enzyme Inhibitors / chemistry
-
Enzyme Inhibitors / isolation & purification*
-
Enzyme Inhibitors / pharmacology*
-
Humans
-
Inhibitory Concentration 50
-
Leukocyte Elastase / antagonists & inhibitors*
-
Leukocyte Elastase / metabolism
-
Magnetic Resonance Spectroscopy
-
Myeloblastin / antagonists & inhibitors
-
Myeloblastin / metabolism
-
Nostoc / chemistry*
-
Peptides, Cyclic / chemistry
-
Peptides, Cyclic / isolation & purification*
-
Peptides, Cyclic / pharmacology*
-
Serine Endopeptidases / metabolism
-
Substrate Specificity
Substances
-
Enzyme Inhibitors
-
Peptides, Cyclic
-
Cathepsins
-
Serine Endopeptidases
-
CTSG protein, human
-
Cathepsin G
-
Leukocyte Elastase
-
Myeloblastin