Affiliation:
1. CRIOBE, UAR CNRS‐EPHE‐UPVD 3278 Université de Perpignan Via Domitia Perpignan France
2. CRM2, UMR UL‐CNRS 7036, Faculté des Sciences et Technologies Université de Lorraine Vandoeuvre‐lès‐Nancy France
3. Institut des Biomolécules Max Mousseron (IBMM) Institut des Biomolécules Max Mousseron (IBMM) Univ Montpellier, CNRS, UM, ENSCM Montpellier France
Abstract
Bergofungin D is a helical peptide of the peptaibol family consisting of 14 amino acids, six of which are the helix inducer aminoisobutyric acid (Aib). In the second third of the sequence, a hydroxyproline causes a bending of the helix and a disruption of the hydrogen bond network, and Aib7 is the only amino acid in this region involved in the hydrogen bond network. Therefore, modification of this residue can serve as a probe to monitor the effect of introducing amino acid substitutions on this more fragile helical turn. To validate this approach, we simplified the original bergofungin D by reducing the number of non‐classical amino acids, replacing the (R)‐isovaleric acid by its enantiomer or an Aib and the hydroxyproline with a proline, respectively, without affecting its secondary structure. Within the modified structure, we replaced Aib7‐Aib8 by its 1,2,3‐triazolodipeptide equivalent or Aib7 by a serine or a dehydrobutyrine. We have reported and analyzed five crystal structures, three of which are new, demonstrating the usefulness of the modified bergofungin D as a probe for monitoring the introduction of amino acid substitutions within a helical structure.
Funder
Université de Perpignan Via Domitia
Ministère de l'Enseignement Supérieur et de la Recherche
Université de Montpellier
Université de Lorraine