Insights into the activity control of the kallikrein-related peptidase 6: small-molecule modulators and allosterism - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Biological Chemistry Année : 2018

Insights into the activity control of the kallikrein-related peptidase 6: small-molecule modulators and allosterism

Résumé

Abstract The activity of kallikrein-related peptidase 6 (KLK6) is deregulated in various diseases such as cancer and neurodegenerative diseases. KLK6 is thus considered as an attractive therapeutical target. In this short report, we depict some novel findings on the regulation of the KLK6 activity. Namely, we identified mechanism-based inhibitors (suicide substrates) from an in-house library of 6-substituted coumarin-3-carboxylate derivatives. In addition, a molecular dynamics study evidenced the allosteric behavior of KLK6 similar to that previously observed for some trypsin-like serine proteases. This allosteric behavior together with the coumarinic scaffold bring new opportunities for the design of KLK6 potent activity modulators, useful as therapeutics or activity-based probes.
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Dates et versions

hal-03997844 , version 1 (20-02-2023)

Identifiants

  • HAL Id : hal-03997844 , version 1

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Feryel Soualmia, Elodie Bosc, Sabrina Aït Amiri, Dirk Stratmann, Viktor Magdolen, et al.. Insights into the activity control of the kallikrein-related peptidase 6: small-molecule modulators and allosterism. Biological Chemistry, 2018, 399 (9), pp.1073-1078. ⟨hal-03997844⟩
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