Design of a functionally equivalent nonglycosylated analog of the glycopeptide antibiotic formaecin I

Kaur, Kanwal J.; Pandey, Sweta; Salunke, Dinakar M.

doi:10.1110/ps.062581707

Cited by 9 publications

(3 citation statements)

References 37 publications

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“…Earlier it has been reported that O-glycosylation has effect on the structure and biological activity of antibacterial peptides as compared to their non-glycosylated counterparts [15,17,[24][25][26][27]. We have shown that conformation provided by carbohydrate can be mimicked by strategically designed amino acids substitutions in the native glycosylated antibacterial peptide and resulted into a functionally equivalent non-glycosylated analog [25].…”

Section: Introductionmentioning

confidence: 80%

“…Earlier it has been reported that formaecin I (I) and monoglycosylated drosocin (M-drosocin) (IX) have higher antibacterial activities than their non-glycosylated counterparts [14,15,25]. The synthetic differently glycosylated peptides of formaecin I and M-drosocin as well as their respective non-glycosylated analogs were evaluated at 25 nmoles for their antibacterial activities against Gramnegative bacterial strains of E. coli ATCC 25922, E. coli BL21λD3, S. typhimurium, and S. typhi Vi + .…”

Section: Antibacterial Activitymentioning

confidence: 99%

“…We have shown that conformation provided by carbohydrate can be mimicked by strategically designed amino acids substitutions in the native glycosylated antibacterial peptide and resulted into a functionally equivalent non-glycosylated analog [25]. Here we examined the effect of different O-linked sugars in two proline-rich glycosylated antibacterial peptides.…”

Section: Introductionmentioning

confidence: 99%

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Glycosylated analogs of formaecin I and drosocin exhibit differential pattern of antibacterial activity

et al. 2011

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The synthetic glycopeptides are interesting model systems to study the effect of O-glycosylation in modulating their function and structure. A series of glycosylated analogs of two antibacterial peptides, formaecin I and drosocin, were synthesized by varying the nature of sugar and its linkage with bioactive peptides to understand the influence of structure variation of glycosylation on their antibacterial activities. Higher antibacterial activities of all glycopeptides compared to their respective non-glycosylated counterparts emphasize in part the importance of sugar moieties in functional implications of these peptides. The consequences of the unique differences among the analogs were apparent on their antibacterial activities but not evident structurally by circular dichroism studies. We have shown that differently glycosylated peptides exhibit differential effect among each other when tested against several Gram-negative bacterial strains. The change of monosaccharide moiety and/or its anomeric configuration in formaecin I and drosocin resulted into decrease in the antibacterial activity in comparison to that of the native glycopeptide, but the extent of decrease in antibacterial activity of glycosylated drosocin analogs was less. Probably, the variation in peptide conformation arising due to topological dissimilarities among different sugars in the same peptide resulting in possible modulation in binding properties appears to be responsible for differences in their antibacterial activities. Indeed, these effects of glycosylation are found to be sequence-specific and depend in the milieu of amino acid residues. Interestingly, none of the carbohydrate variants affected the basic property of these peptides, which is non-hemolytic and non-toxicity to eukaryotic cells.

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