Development of helix-stabilized antimicrobial peptides composed of lysine and hydrophobic α, α-disubstituted α-amino acid residues. Issue 17 (1st September 2017)

• Record Type: Journal Article
• Authors: Misawa, Takashi; Imamura, Mitsuyoshi; Ozawa, Yuto; Haishima, Kazuchika; Kurihara, Masaaki; Kikuchi, Yutaka; Demizu, Yosuke
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 17(2017)
• Page Start: 3950
• Page End: 3953
• Publication Date: 2017-09-01
• Subjects: α, α-Disubstituted α-amino acid -- Helical peptide -- Circular dichroism -- Antimicrobial activity; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.07.074
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Lysine-based amphipathic nonapeptides, including homochiral peptides [Ac-(l -Lys-l -Lys-Xaa)3 -NH2 (Xaa = Gly, Ala, Aib, Ac5 c, or Ac6 c) and Ac-(d -Lys-d -Lys-Aib)3 -NH2 ], a heterochiral peptide [Ac-(l -Lys-d -Lys-Aib)3 -NH2 ], and a racemic mixture of diastereomeric peptides [Ac-( rac -Lys- rac -Lys-Aib)3 -NH2 ] were designed and synthesized to investigate the relationship between their preferred secondary structures and their antimicrobial activity. Peptide5, [Ac-(l -Lys-l -Lys-Ac6 c)3 -NH2 ] formed a stable α-helical structure and exhibited strong activity against Gram-negative bacteria ( Escherichia coli and Pseudomonas aeruginosa ).