Investigation into the P sub(3) Binding Domain of m-Calpain Using Photoswitchable Diazo- and Triazene-dipeptide Aldehydes: New Anticataract Agents

The photoswitchable N-terminal diazo and triazene-dipeptide aldehydes 8a-d, 10a,b, and 17a,b present predominantly as the (E)-isomer, which purportedly binds deep in the S sub(3) pocket of calpain. All compounds are potent inhibitors of m-calpain, with 8b being the most active (IC sub(50) of 35 nM)....

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Bibliographic Details
Published in:Journal of medicinal chemistry 2007-06, Vol.50 (12), p.2916-2920
Main Authors: Abell, AD, Jones, MA, Neffe, A T, Aitken, S G, Cain, T P, Payne, R J, McNabb, S B, Coxon, J M, Stuart, B G, Pearson, D, Lee, HY-Y, Morton, J D
Format: Article
Language:English
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Summary:The photoswitchable N-terminal diazo and triazene-dipeptide aldehydes 8a-d, 10a,b, and 17a,b present predominantly as the (E)-isomer, which purportedly binds deep in the S sub(3) pocket of calpain. All compounds are potent inhibitors of m-calpain, with 8b being the most active (IC sub(50) of 35 nM). The diazocontaining inhibitors 8a, 8c, and 10a were irradiated at 340 nm to give a photostationary state enriched in the (Z)-isomer, and in all cases, these were less active. The most water soluble triazene 17a (IC sub(50) of 90 nM) retards calpain-induced cataract formation in lens culture.
ISSN:0022-2623
DOI:10.1021/jm061455n