A new synthetic all-D-peptide with high bacterial and low mammalian cytotoxicity.
Using the synthetic alpha-helical peptide ((RLA)(2)R)(2) as a model the effect of net charge, helicity, and epimeric nature of the peptide on bactericidal potency has been examined. Both the nature and the extent of the net charge were shown to be relatively important for antibacterial activity. The loss of the structured character of the peptide resulted in reducing the activity. The all-D-peptide appeared to be a remarkably strong bacteriostatic agent with MIC <1 microM against Escherichia coli. The peptide was neither hemolytic nor cytotoxic, which in conjunction with data on its stability to enzymatic degradation makes this peptide very attractive in terms of designing new bactericidal agents on the basis of (D)((RLA)(2)R)(2).
Ryadnov
Maxim G
MG
Institute of Protein Research, Russian Academy of Sciences, 142290 Puschino, Moscow Region, Russia. depmax@biols.sussex.ac.uk
Degtyareva
Olga V
OV
Kashparov
Ivan A
IA
Mitin
Yuri V
YV
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D004912:Erythrocytes / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D010446:Peptide Fragments / Q000737:chemistry; D017433:Protein Structure, Secondary; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D010446:Peptide Fragments