Investigation of the N-Terminus Amino Function of Arg10-Teixobactin

• Main Authors: Shimaa A. H. Abdel Monaim, Sikabwe Noki, Estelle J. Ramchuran, Ayman El-Faham, Fernando Albericio, Beatriz G. de la Torre
• Format: Article
• Language: English
• Published: MDPI AG 2017-09-01
• Series: Molecules
• Subjects: antimicrobial peptides; teixobactin; lipophilicity; solid-phase peptide synthesis; cyclic depsipeptides
• Online Access: https://www.mdpi.com/1420-3049/22/10/1632

Teixobactin is a recently described antimicrobial peptide that shows high activity against gram-positive bacteria as well as mycobacterium tuberculosis. Due to both its structure as a head-to-side chain cyclodepsipeptide and its activity, it has attracted the attention of several research groups. In this regard, a large number of analogs with substitutions in both the cycle and the tail has been described. Here, we report the contribution of the N-terminus residue, N-Me-d-Phe, to the activity of Arg10-teixobactin. On the basis of our findings, we conclude that the N-terminus accepts minimum changes but not the presence of long alkyl chains. The presence of a positive charge is a requirement for the activity of the peptide. Furthermore, acylation of the N-terminus leads to total loss of activity.