title: Glycosylated analogs of formaecin I and drosocin exhibit differential pattern of antibacterial activity.
abstract: 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.
authors.affiliation: Structural Biology Unit, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067, India.
authors.forename: Sariya
authors.initials: S
authors.lastname: Talat
authors.forename: Menithalakshmi
authors.initials: M
authors.lastname: Thiruvikraman
authors.forename: Saroj
authors.initials: S
authors.lastname: Kumari
authors.forename: Kanwal J
authors.initials: KJ
authors.lastname: Kaur
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D001419:Bacteria / Q000187:drug effects; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D016923:Cell Death / Q000187:drug effects; D002942:Circular Dichroism; D004912:Erythrocytes / Q000187:drug effects; D006020:Glycopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006023:Glycoproteins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006031:Glycosylation / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D019476:Insect Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D051381:Rats
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D006020:Glycopeptides; D006023:Glycoproteins; D019476:Insect Proteins; C111162:formaecin 1 protein, Myrmecia gulosa; C082117:drosocin