2 research outputs found
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
Lysine Scanning of Arg<sub>10</sub>–Teixobactin: Deciphering the Role of Hydrophobic and Hydrophilic Residues
Teixobactin
is a recently discovered antimicrobial cyclodepsipeptide
with good activity against Gram positive bacteria. Taking Arg<sub>10</sub>–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