Substitution of the GalNAc-α-O-Thr¹¹ residue in drosocin with O-linked glyco-peptoid residue: Effect on antibacterial activity and conformational change

One of the obvious disadvantages of natural peptides is their liability to proteases. Among the several solutions for this issue, peptoids or oligomers of N-substituted glycine have emerged as a promising tool that may enhance the stability of proteolysis-susceptible natural peptides. We have synthe...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2011-10, Vol.21 (20), p.6148-6153
Main Authors: Ahn, Mija, Murugan, Ravichandran N, Nan, Yong Hai, Cheong, Chaejoon, Sohn, HoIk, Kim, Eun-Hee, Hwang, Eunha, Ryu, Eun Kyoung, Kang, Shin Won, Shin, Song Yub, Bang, Jeong Kyu
Format: Article
Language:English
Subjects:
Animals
Anti-Bacterial Agents - chemistry
Anti-Bacterial Agents - pharmacology
Antibacterial agents
antibacterial properties
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antimicrobial Cationic Peptides - chemistry
Antimicrobial Cationic Peptides - pharmacology
Biological and medical sciences
Drosophila melanogaster - chemistry
Escherichia coli - drug effects
Escherichia coli Infections - drug therapy
Glycopeptides - chemistry
Glycopeptides - pharmacology
Insect Proteins - chemistry
Insect Proteins - pharmacology
Medical sciences
peptides
Peptoids - chemistry
Peptoids - pharmacology
Pharmacology. Drug treatments
proteinases
Structure-Activity Relationship
structure-activity relationships
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Summary:One of the obvious disadvantages of natural peptides is their liability to proteases. Among the several solutions for this issue, peptoids or oligomers of N-substituted glycine have emerged as a promising tool that may enhance the stability of proteolysis-susceptible natural peptides. We have synthesized the drosocin and its glyco-peptoid analogues linked O-GalNAc at the Thr¹¹ residue. One of our glyco-peptoid analogues showed an increased antibacterial activity by the modification of the Thr¹¹ residue with glyco-peptoid. Structure–activity relationship studies revealed that the antibacterial activity by glyco-peptoid drosocin requires three key elements: free hydroxyl group on the carbohydrate moiety, γ-methyl group of the Thr¹¹ residue derivative and (S)-configuration over (R)-configuration.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2011.08.012