Investigation of the N-terminus amino functional of Arg10-Teixobactin

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

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

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

Converting Teixobactin into a Cationic Antimicrobial Peptide (AMP)

Teixobactin is a head to side chain cyclodepsipeptide that contains two positive charges. One is found in the cycle, as a result of the presence of the guanidino-unusual amino acid L-<i>allo</i>-End, while the other is at the <i>N</i>-terminal. Here we introduce 26 new Teixobactin analogues with an increasing number of positive charges. In an attempt to fine-tune the biological activity of Teixobactin, we examined the effect of cationicity on the SAR of these analogues. The maximum number of positive charges to maintain the activity are three to four. Analogues with five positive charges show the lowest activity

Structure-Activity Relationship of Arg10-Teixobactin: A Recently Discovered Antimicrobial Peptide

The emergence of multidrug resistant bacteria has a direct impact on global public health due to the reduced potency of existing antibiotics against pathogens [1]. [...

Lysine Scanning of Arg₁₀–Teixobactin: Deciphering the Role of Hydrophobic and Hydrophilic Residues

Teixobactin is a recently discovered antimicrobial cyclodepsipeptide with good activity against Gram positive bacteria. Taking Arg₁₀–teixobactin as a reference, where the nonproteinogenic residue l-allo-enduracididine was substituted by arginine, a lysine scan was performed to identify the importance of keeping the balance between hydrophilic and hydrophobic amino acids for the antimicrobial activities of this peptide family. Thus, the substitution of four isoleucine residues present in the natural sequence by lysine led to a total loss of activity. On the other hand, the substitution of the polar noncharged residues and alanine by lysine allowed us to keep and in some cases to improve the antimicrobial activity