|
KMID : 0043320180410111092
|
|
Archives of Pharmacal Research
2018 Volume.41 No. 11 p.1092 ~ p.1097
|
|
|
Effects of lysine-to-arginine substitution on antimicrobial activity of cationic stapled heptapeptides
|
|
Luong Huy X.
Kim Do-Hee
Lee Bong-Jin
Kim Young-Woo
|
|
|
Abstract
|
|
|
|
We previously reported a series of amphipathic helices of stapled heptapeptides as membrane-lytic antimicrobial peptides. These peptides possess three lysine residues as the sole cationic amino acid residues in their hydrophilic face of the helix. Lysine-to-arginine substitution is often shown to increase antimicrobial activity of many natural AMPs due to the more favorable interactions of guanidinium moiety of arginine with membranes. In an effort to further improve the pharmacological properties of our novel AMP series, we here examined the impact of lysine-to-arginine substitution on their structures and antimicrobial and hemolytic activities. Our results indicate that the lysine-to-arginine substitution does not always guarantee enhancement in the antimicrobial potency of AMPs. Instead, we observed varied potency and selectivity depending on the number of substitutions and the positions substituted. Our results imply that, in the given helical scaffold stabilized by a hydrocarbon staple, antimicrobial potency and selectivity are influenced by a complex effect of various structural and chemical changes accompanied by lysine-to-arginine substitution rather than solely by the type of cationic residue. These data show potential for use in our scaffold-assisted development of short, selective, and metabolically stable AMPs.
|
|
|
KEYWORD
|
|
|
Antimicrobial peptides, α-Helix, Stapled peptides, Amphipathic peptides, Proteolytic resistance
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|