Discovery of Trp-His and His-Arg analogues as new structural classes of short antimicrobial peptides.

Abstract

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.

• Authors: Rohit K Sharma, Ravi P Reddy, Werner Tegge, Rahul Jain
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 52 Issue 23 Pg. 7421-31 (Dec 10 2009) ISSN: 1520-4804 [Electronic] United States
• PMID: 19655779 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimicrobial Cationic Peptides
• Dipeptides
• tryptophyl-histidine

Topics

• Antimicrobial Cationic Peptides (chemical synthesis, chemistry, pharmacology)
• Bacteria (drug effects)
• Dipeptides (chemical synthesis, chemistry, pharmacology)
• Drug Discovery
• Fungi (drug effects)
• Microbial Sensitivity Tests