Fiorino Ferdinando, Gil-Parrado Shirley, Assfalg-Machleidt Irmgard, Machleidt Werner, Moroder Luis
Max-Planck-Institut für Biochemie, Am Klopferspitz 18, D-82152 Martinsried, Germany.
J Pept Sci. 2007 Jan;13(1):70-3. doi: 10.1002/psc.790.
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.
普遍存在的钙蛋白酶，即μ-钙蛋白酶和m-钙蛋白酶，参与多种重要的（病理）生理过程，因此细胞可渗透的特异性抑制剂是确定钙蛋白酶在细胞和动物模型中作用的重要工具。已知一种源自人钙蛋白酶抑制域1外显子B的合成N-乙酰化27肽是最有效且选择性的钙蛋白酶可逆抑制剂。为提高这种肽类抑制剂的膜通透性，在其N端进行了延伸，或将其与穿膜肽的C端7肽片段通过二硫键连接，穿膜肽是一种用于生物活性化合物细胞膜转运的成熟载体。尽管穿膜肽序列较短，但两种构建体均显示出细胞通透性增加，并保留了其全部钙蛋白酶抑制效力。
