A new cell-permeable calpain inhibitor.
The ubiquitous calpains, mu- and m-calpain, are implicated in a variety of vital (patho)physiological processes and therefore cell-permeable specific inhibitors represent important tools for defining the role of calpains in cells and animal models. A synthetic N-acetylated 27-mer peptide derived from exon B of the human calpastatin inhibitory domain 1 is known to be the most potent and selective reversible inhibitor of calpains. To improve the membrane permeability of this peptidic inhibitor, it was N-terminally extended with or disulfide-linked to the C-terminal 7-mer fragment of penetratin, a well-established vector for cell membrane translocation of bioactive compounds. Despite the shorter penetratin sequence, both constructs showed increased cell permeability and retained their full calpain inhibitory potency.
Fiorino
Ferdinando
F
Max-Planck-Institut für Biochemie, Am Klopferspitz 18, D-82152 Martinsried, Germany.
Gil-Parrado
Shirley
S
Assfalg-Machleidt
Irmgard
I
Machleidt
Werner
W
Moroder
Luis
L
D000595:Amino Acid Sequence; D002135:Calcium-Binding Proteins / Q000737:chemistry; D002154:Calpain / Q000037:antagonists & inhibitors*; D002352:Carrier Proteins / Q000737:chemistry; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D057846:Cell-Penetrating Peptides; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D006023:Glycoproteins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D006023:Glycoproteins; C039304:calpain inhibitors; C033668:calpastatin; C414409:penetratin; D002154:Calpain