title: Design of a functionally equivalent nonglycosylated analog of the glycopeptide antibiotic formaecin I.
abstract: Various nonglycosylated analogs were designed in order to explore the role of glycosylation in formaecin I, an antibacterial glycopeptide of insect origin. The functional behavior of a designed nonglycosylated analog (P(7),endo P(8a),DeltaT(11))formaecin I was found to be similar to that of native glycosylated peptide. Both the peptides showed similar antibacterial activities against Escherichia coli and Salmonella strains. The designed nonglycosylated analog (P(7),endo P(8a),DeltaT(11))formaecin I has low binding affinity to LPS identical to that of native glycopeptide, formaecin I. Both the peptides have similar killing kinetics and are nontoxic to erythrocytes. Formaecin I and designed nonglycosylated (P(7),endo P(8a),DeltaT(11))formaecin I have no definite conformational features associated with them. The glycosylated residue of threonine in formaecin I and proline residues in designed peptide [(P(7),endo P(8a),DeltaT(11))formaecin I], possibly help in stabilizing the correct conformation that facilitates presentation of the peptide to its receptor. It is evident that a functionally equivalent nonglycosylated analog of native glycosylated antibacterial peptide can be designed by strategically modifying the sequence.
authors.affiliation: Structural Biology Unit, National Institute of Immunology, Aruna Asal Ali Marg, New Delhi 110-067, India. kanwal@nii.res.in
authors.forename: Kanwal J
authors.initials: KJ
authors.lastname: Kaur
authors.forename: Shashank
authors.initials: S
authors.lastname: Pandey
authors.forename: Dinakar M
authors.initials: DM
authors.lastname: Salunke
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004926:Escherichia coli / Q000187:drug effects; D006020:Glycopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006023:Glycoproteins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006031:Glycosylation; D006461:Hemolysis / Q000187:drug effects; D019476:Insect Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008969:Molecular Sequence Data; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects; D016415:Sequence Alignment
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D006020:Glycopeptides; D006023:Glycoproteins; D019476:Insect Proteins; C111162:formaecin 1 protein, Myrmecia gulosa