Glycine Substitution Reduces Antimicrobial Activity
and Helical Stretch of diPGLa‑H in Lipid Micelles
M.-A. Sani
C. Saenger
D. Juretic
F. Separovic
10.1021/acs.jpcb.7b03067.s001
https://acs.figshare.com/articles/journal_contribution/Glycine_Substitution_Reduces_Antimicrobial_Activity_and_Helical_Stretch_of_diPGLa_H_in_Lipid_Micelles/4954154
With
the rise in antibiotic resistance, antimicrobial peptides
(AMPs) show promise for therapeutic development, but higher specificity
is required. PGLa-H is a naturally occurring decapeptide, reported
to have moderate antibacterial activity and low hemolytic activity,
with its sequence being identical to that of the C-terminal fragment
of highly selective AMP, PGLa. DiPGLa-H, a sequential tandem repeat
of PGLa-H, and Kiadin, an analogue with a Val to Gly substitution
at position 15, display improved in vitro bactericidal activity against
both Gram-negative and Gram-positive pathogens, with generally low
toxicity for human cells. Despite Gly being a more flexible residue,
NMR structural studies showed little difference in structure and dynamics
between the two peptides for the first 14 residues, with somewhat
greater flexibility in the C-terminus of Kiadin resulting in a tighter
structure of the peptide in the presence of sodium dodecyl sulfate
micelles. AMPs found in organisms often exhibit minimal amino acid
mutations, and such small differences in peptide conformation may
be utilized to design more selective AMPs.
2017-04-20 00:00:00
acid mutations
Antimicrobial Activity
Helical Stretch
Glycine Substitution
14 residues
antimicrobial peptides
bactericidal activity
C-terminal fragment
Gram-positive pathogens
NMR
sequential tandem
antibiotic resistance
Kiadin
PGLa-H
AMP
Lipid Micelles
show promise
sodium dodecyl sulfate micelles
peptide conformation
Gly substitution