Discovery of Trp-His and His-Arg analogues as new structural classes of short antimicrobial peptides.
Naturally occurring antimicrobial peptides contain a large number of amino acid residues, which limits their clinical applicability. In search of short antimicrobial peptides, which represent a possible alternative for lead structures to fight antibiotic resistant microbial infections, a series of synthetic peptide analogues based on Trp-His and His-Arg structural frameworks have been prepared and found to be active against several Gram-negative and Gram-positive bacterial strains as well as against a fungal strain with MIC values of the most potent structures in the range of 5-20 microg/mL ((IC(50) in the range of 1-5 microg/mL). The synthesized peptides showed no cytotoxic effect in an MTT assay up to the highest test concentration of 200 microg/mL. A combination of small size, presence of unnatural amino acids, high antimicrobial activity, and absence of cytotoxicity reveals the synthesized Trp-His and His-Arg analogues as promising candidates for novel antimicrobial therapeutics.
Sharma
Rohit K
RK
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, SAS Nagar 160 062, Punjab, India.
Reddy
Ravi P
RP
Tegge
Werner
W
Jain
Rahul
R
D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D055808:Drug Discovery; D005658:Fungi / Q000187:drug effects; D008826:Microbial Sensitivity Tests
D023181:Antimicrobial Cationic Peptides; D004151:Dipeptides; C509582:tryptophyl-histidine