Functional and Structural Characterization of Drosocin and its Derivatives Linked O-GalNAc at Thr¹¹Residue

Abstract

Antimicrobial peptides have recently gained the much attention because of their ability to make defense system from attacking bacterial infections. Drosocin has been considered as very attractive antibiotic agents because of low toxicity against human erythrocytes and active at the low concentration. We have studied the structureactivity relationship of a glycopeptide drosocin focused on the N-acetyl-D-galactoside at Thr 11 residue. Based on the radial diffusion assay, we found that the acetylation of carbohydrate moiety increased the antimicrobial activity and the Pro 10 , present in the middle of drosocin plays an important role in the antimicrobial activity. Our results provide a good lead compound for further studies on the design of drosocin-based analogues targeting glyco linked Thr site.

Structural basis for translation inhibition by the glycosylated antimicrobial peptide Drosocin fromDrosophila melanogaster

“…4e ). Mutation of Pro10 to Ala abolishes antimicrobial activity (Ahn et al, 2011b), presumably by altering the conformation of the peptide within this region. Ser12 of Dro1 can hydrogen bond directly with U746 and form a water-mediated interaction with G748 ( Fig.…”

“…Synthetic drosocin lacking O-glycosylation is less active than the native compounds, suggesting that the post-translational modification is necessary for full activity (Bulet et al, 1993; Bulet et al, 1999; Bulet et al, 1996; Gobbo et al, 2002; Hoffmann et al, 1999). Indeed, many studies have demonstrated that a variety of synthetic drosocin derivatives with varying sugar moieties maintain good antimicrobial activity, generally better than the unmodified form (Ahn et al, 2011a; Ahn et al, 2011b; Gobbo et al, 2002; Lele et al, 2015a; Marcaurelle et al, 1998; Otvos et al, 2000; Rodriguez et al, 1997; Talat et al, 2011). Although NMR and CD experiments suggest that both the modified and unmodified forms of drosocin adopt extended conformations in solution (Bulet et al, 1996; Gobbo et al, 2002; Lele et al, 2015a; McManus et al, 1999; Talat et al, 2011), the presence of the modification has nevertheless been proposed to help drosocin maintain an extended conformation to facilitate binding to its intracellular target (Bulet et al, 1999; Gobbo et al, 2002; McManus et al, 1999).…”

Insect Antimicrobial Peptides, a Mini Review

“…Increasing the number of positively charged amino acids or changing their position in the peptide chain can affect the secondary structure of the AMPs, thereby further affecting their antibacterial activity. Thus, the combination of charge, hydrophobicity, and length of the peptide is important for the antimicrobial activity of AMPs [ 27 , 28 , 29 ].…”

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2011–2012

“…linked O-GalNAc at Thr 11 residue TOF Synthesis, functional and structural characterization (Ahn et al, 2011a) Epoxidized fatty acid esters of sucrose TOF (CHCA) conditions (Pan et al, 2011b) Fluoro-sugar-terminated oligosaccharides TOF For investigating sequence specificity of carbohydrate polymerase (Brown et al, 2012a) Galacto-oligosaccharides R-TOF (DHB + NaI)…”