Abstract
The natural product miraziridine A isolated from the marine sponge Theonella aff. mirabilis unifies within one molecule three structurally privileged elements: (i) (2R,3R)-aziridine-2,3-dicarboxylic acid, (ii) (3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid (statine), and (iii) (E)-(S)-4-amino-7-guanidino-hept-2-enoic acid (vinylogous arginine). The alignment of them realized in the tetrapetide allows for a simultaneous inhibition of the proteolytic activity of trypsin-like serine proteases, papain-like cysteine proteases, and pepsin-like aspartyl proteases. Therefore, this unique compound represents a blueprint for the design of protease class-spanning inhibitors.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Aziridines / chemistry
-
Aziridines / isolation & purification
-
Aziridines / pharmacology*
-
Cathepsin B / antagonists & inhibitors*
-
Cathepsin L
-
Cathepsins / antagonists & inhibitors*
-
Cysteine Endopeptidases
-
Endopeptidases / classification*
-
Molecular Structure
-
Oligopeptides / chemistry
-
Oligopeptides / isolation & purification
-
Oligopeptides / pharmacology*
-
Pepsin A / antagonists & inhibitors*
-
Porifera / chemistry
-
Protease Inhibitors / chemistry
-
Protease Inhibitors / isolation & purification
-
Protease Inhibitors / pharmacology*
-
Trypsin / metabolism*
Substances
-
Aziridines
-
Oligopeptides
-
Protease Inhibitors
-
miraziridine A
-
Cathepsins
-
Endopeptidases
-
Trypsin
-
Cysteine Endopeptidases
-
Cathepsin B
-
Cathepsin L
-
Pepsin A