Abstract
Inhibition of the cysteine protease calpain is a promising strategy for the treatment of muscular dystrophies including Duchenne Muscular Dystrophy. For the treatment to be effective, uptake of the inhibitors into the muscle cells is a prerequisite. A series of α-ketoamide calpain inhibitors carrying various muscle cell targeting capping groups was synthesized. Compounds with charged or highly polar targeting groups were not able to cross the cellular membrane. Introduction of lipoic acid as end cap yielded cell permeable calpain inhibitors with nanomolar potency.
Keywords: Calpain inhibitor, ketoamide, duchenne muscular dystrophy, lipoic acid
Letters in Drug Design & Discovery
Title: Synthesis and Evaluation of Calpain Inhibitors Carrying Muscle Cell Targeting Groups
Volume: 3 Issue: 3
Author(s): P. Weyermann, H. Herzner, C. Lescop, H. Siendt, R. Bolliger, M. Hennebohle, C. Rummey, A. Briguet, I. Courdier-Fruh, M. Erb, M. Foster, J.P. Magyar, A. von Sprecher and T. Meier
Affiliation:
Keywords: Calpain inhibitor, ketoamide, duchenne muscular dystrophy, lipoic acid
Abstract: Inhibition of the cysteine protease calpain is a promising strategy for the treatment of muscular dystrophies including Duchenne Muscular Dystrophy. For the treatment to be effective, uptake of the inhibitors into the muscle cells is a prerequisite. A series of α-ketoamide calpain inhibitors carrying various muscle cell targeting capping groups was synthesized. Compounds with charged or highly polar targeting groups were not able to cross the cellular membrane. Introduction of lipoic acid as end cap yielded cell permeable calpain inhibitors with nanomolar potency.
Export Options
About this article
Cite this article as:
Weyermann P., Herzner H., Lescop C., Siendt H., Bolliger R., Hennebohle M., Rummey C., Briguet A., Courdier-Fruh I., Erb M., Foster M., J.P. Magyar , A. von Sprecher and T. Meier , Synthesis and Evaluation of Calpain Inhibitors Carrying Muscle Cell Targeting Groups, Letters in Drug Design & Discovery 2006; 3 (3) . https://dx.doi.org/10.2174/157018006776286916
DOI https://dx.doi.org/10.2174/157018006776286916 |
Print ISSN 1570-1808 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-628X |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers