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Article Dans Une Revue Biomedicine and Pharmacotherapy Année : 2023

Structure-function relationship of new peptides activating human Nav1.1

Cécile Caumes
  • Fonction : Auteur
Kuldip Khakh
  • Fonction : Auteur
Steve Peigneur
  • Fonction : Auteur
Sophia Lin
  • Fonction : Auteur
J.P. Johnson
Jan Tytgat
  • Fonction : Auteur
Charles Cohen
  • Fonction : Auteur
Rémy Béroud
  • Fonction : Auteur
Frank Bosmans
Céline Landon

Résumé

Na v 1.1 is an important pharmacological target as this voltage-gated sodium channel is involved in neurological and cardiac syndromes. Channel activators are actively sought to try to compensate for haploinsufficiency in several of these pathologies. Herein we used a natural source of new peptide compounds active on ion channels and screened for drugs capable to inhibit channel inactivation as a way to compensate for decreased channel function. We discovered that JzTx-34 is highly active on Na v 1.1 and subsequently performed a full structureactivity relationship investigation to identify its pharmacophore. These experiments will help interpret the mechanism of action of this and formerly identified peptides as well as the future identification of new peptides. We also reveal structural determinants that make natural ICK peptides active against Na v 1.1 challenging to synthesize. Altogether, the knowledge gained by this study will help facilitate the discovery and development of new compounds active on this critical ion channel target.
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Licence : CC BY ND - Paternité - Pas de modifications

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hal-04224866 , version 1 (02-10-2023)

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Paternité - Pas de modifications

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Ludivine Lopez, Stephan de Waard, Hervé Meudal, Cécile Caumes, Kuldip Khakh, et al.. Structure-function relationship of new peptides activating human Nav1.1. Biomedicine and Pharmacotherapy, 2023, 165, pp.115173. ⟨10.1016/j.biopha.2023.115173⟩. ⟨hal-04224866⟩
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