Design of a functionally equivalent nonglycosylated analog of the glycopeptide antibiotic formaecin I.
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.
Kaur
Kanwal J
KJ
Structural Biology Unit, National Institute of Immunology, Aruna Asal Ali Marg, New Delhi 110-067, India. kanwal@nii.res.in
Pandey
Shashank
S
Salunke
Dinakar M
DM
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
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D006020:Glycopeptides; D006023:Glycoproteins; D019476:Insect Proteins; C111162:formaecin 1 protein, Myrmecia gulosa