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Identification and characterization of novel lipophilic antimicrobial peptides derived from naturally occurring proteins

DOI: 10.1007/s10989-006-9033-4 DOI Help

Authors: Rohannah Hussain (Diamond Light Source; Kings College London) , Christopher L. Joannou (Kings College London) , Giuliano Siligardi (Diamond Light Source)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: International Journal Of Peptide Research And Therapeutics , VOL 12 (3) , PAGES 269-273

State: Published (Approved)
Published: September 2006

Abstract: Microbes are increasingly developing defensive mechanisms against known drugs via mutations. There are signs of emergence of superbugs immune to most known antibiotics available. The need for a new class of drugs to Counteract this problem is of paramount importance for continued general well being of mankind. A new class of drugs, antimicrobial peptides, has not been fully exploited primarily due to high cytotoxicity, poor lipophilicity preventing systemic distribution and stability. We have synthesised 9-amino acid residue cationic peptides RH01 and RH02 lipidated with myristoyl and octyl groups respectively. These peptides exhibited potent antimicrobial activity and low cytotoxicity. The lipopeptide RHO I has antimicrobial activity against a broad range of microorganisms including bacteria. yeast and filamentous fungi with greatest activity toward Gram-positive bacteria, including S. aureus MRSA stain, MIC's ranging between 2-8 mu M. The MIC for Gram-negative bacteria was higher ranging from between 30-250 mu M. RH01 also had antimicrobial activity towards fungi showing good activity against the pathogenic yeast Candida albicans but was less active towards the filamentous fungi Aspergillus niger. The antimicrobial activity of RH01 as a measure of Ki((50)) for E. coli and S. aureus was 35-60 mu M and 3-7 mu M, respectively. In-house data showed the compound is bactericidal even at higher bacteria concentration. The octylated lipopeptide RH02 has similar activities towards S. aureus (3.3 mu M) and E coli (53.3 mu M) as the myristolated RH01. There was no haemolytic activity of the lipopeptide RH01 towards human blood. Acute intravenous toxicity study in mice showed that both RH01 and RH02 induced no macroscopic abnormalities at their highest non-lethal dose of 75 mg/kg and 150 mg/kg bodyweight, respectively.

Diamond Keywords: Bacteria

Subject Areas: Biology and Bio-materials, Medicine

Technical Areas:

Added On: 16/08/2010 15:33

Discipline Tags:

Pathogens Antibiotic Resistance Health & Wellbeing Drug Discovery Life Sciences & Biotech

Technical Tags: