Miraziridine A: natures blueprint towards protease class-spanning inhibitors.
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.
Schaschke
Norbert
N
Max-Planck-Institut für Biochemie, D-82152 Martinsried, Germany. schaschk@biochem.mpg.de
D000818:Animals; D001388:Aziridines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002401:Cathepsin B / Q000037:antagonists & inhibitors*; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D003546:Cysteine Endopeptidases; D010450:Endopeptidases / Q000145:classification*; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010434:Pepsin A / Q000037:antagonists & inhibitors*; D011161:Porifera / Q000737:chemistry; D011480:Protease Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014357:Trypsin / Q000378:metabolism*
D001388:Aziridines; D009842:Oligopeptides; D011480:Protease Inhibitors; C490847:miraziridine A; D002403:Cathepsins; D010450:Endopeptidases; D014357:Trypsin; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D056668:Cathepsin L; D010434:Pepsin A