title: Poly-arginine-fused calpastatin peptide, a living cell membrane-permeable and specific inhibitor for calpain.
abstract: Calpain, a Ca2+-dependent neutral protease, is highly related to the pathogenesis of a variety of disorders and its inhibitors offer potential for therapeutic intervention. General calpain inhibitors, however, have the disadvantage of a lack of specificity or poor cellular permeability or oxidization under physiological conditions. Here, we developed a membrane-permeable specific calpain inhibitor by fusing calpastatin peptide (CS) and 11 poly-arginine peptides (11R). The 11R-fused CS (11R-CS) effectively penetrated across the plasma membrane of living neurons and significantly inhibited calpain activity in the cells.
authors.affiliation: Department of Physiology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Wu
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Tomizawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Matsushita
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Lu
authors.forename: Sheng-Tian
authors.initials: ST
authors.lastname: Li
authors.forename: Hideki
authors.initials: H
authors.lastname: Matsui
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D002154:Calpain / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D051381:Rats; D013379:Substrate Specificity
chemical_list: D002135:Calcium-Binding Proteins; D015853:Cysteine Proteinase Inhibitors; D010455:Peptides; C015462:polyarginine; C033668:calpastatin; D002154:Calpain