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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

IMPACT FACTOR 2018: 3.014
5-year IMPACT FACTOR: 3.162

CiteScore 2018: 3.09

SCImago Journal Rank (SJR) 2018: 1.482
Source Normalized Impact per Paper (SNIP) 2018: 0.820

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Volume 384, Issue 3


Calpastatin Exon 1B-Derived Peptide, a Selective Inhibitor of Calpain: Enhancing Cell Permeability by Conjugation with Penetratin

S. Gil-Parrado / I. Assfalg-Machleidt / F. Fiorino / D. Deluca / D. Pfeiler / N. Schaschke / L. Moroder / W. Machleidt
Published Online: 2005-06-01 | DOI: https://doi.org/10.1515/BC.2003.045


The ubiquitous calpains, u- and m-calpain, have been implicated in essential physiological processes and various pathologies. Cell-permeable specific inhibitors are important tools to elucidate the roles of calpains in cultivated cells and animal models. The synthetic Nacetylated 27-mer peptide derived from exon B of the inhibitory domain 1 of human calpastatin (CP1B) is unique as a potent and highly selective reversible calpain inhibitor, but is poorly cell-permeant. By addition of N-terminal cysteine residues we have generated a disulfide-conjugated CP1B with the cell-penetrating 16-mer peptide penetratin derived from the third helix of the Antennapedia homeodomain protein. The inhibitory potency and selectivity of CP1B for calpain versus cathepsin B and L, caspase 3 and the proteasome was not affected by the conjugation with penetratin. The conjugate was shown to efficiently penetrate into living LCLC 103H cells, since it prevents ionomycin-induced calpain activation at 200-fold lower concentration than the non-conjugated inhibitor and is able to reduce calpain triggered apoptosis of these cells. Penetratin-conjugated CP1B seems to be a promising alternative to the widely used cell-permeable peptide aldehydes (e.g. calpain inhibitor I) which inhibit the lysosomal cathepsins and partially the proteasome as well or even better than the calpains.

About the article

Published Online: 2005-06-01

Published in Print: 2003-03-14

Citation Information: Biological Chemistry, Volume 384, Issue 3, Pages 395–402, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2003.045.

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