Effects of Aib residues insertion on the structural–functional properties of the frog skin-derived peptide esculentin-1a(1–21)NH₂

详细信息    查看全文

• 作者：Barbara Biondi ; Bruno Casciaro ; Antonio Di Grazia ; Floriana Cappiello…
• 关键词：Antimicrobial peptides ; α ; Aminoisobutyric acid ; Gram ; positive bacteria ; NMR
• 刊名：Amino Acids
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：49
• 期：1
• 页码：139-150
• 全文大小：
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biochemistry, general; Analytical Chemistry; Biochemical Engineering; Life Sciences, general; Proteomics; Neurobiology;
• 出版者：Springer Vienna
• ISSN：1438-2199
• 卷排序：49

文摘

Antimicrobial peptides (AMPs) play a key role in the defence mechanism of living organisms against microbial pathogens, displaying both bactericidal and immunomodulatory properties. They are considered as a promising alternative to the conventional antibiotics towards which bacteria are becoming highly resistant. Recently, a derivative of the frog skin AMP esculentin-1a, esculentin-1a(1–21)NH₂ [Esc(1–21)], showed a strong and fast membranolytic activity against Gram-negative bacteria but with a lower efficacy against Gram-positive ones. Here, with the aim to increase the α-helicity of Esc(1–21) and the expected potency against Gram-positive bacteria, we designed an analog bearing three α-aminoisobutyric acid (Aib) residues at positions 1, 10, and 18 of its primary structure. We demonstrated that the incorporation of Aib residues: (1) promoted the α-helix conformation of Esc(1–21), as confirmed by circular dichroism and two-dimensional nuclear magnetic resonance spectroscopies; (2) was sufficient to make this analog more active than the parent peptide against several Gram-positive bacterial strains without affecting its activity against Gram-negative bacteria; and (3) resulted to be devoid of toxic effect toward epithelial cells at the active antimicrobial concentrations. These results suggest that replacement of L-amino acids with Aib residues has beneficial effects on the structure and properties of the membrane-active peptide Esc(1–21), making it a better candidate for the design and development of selective drugs against Gram-positive bacteria.