Database Filtering Tech Leads to Synthesis of Potent New Anti-MRSA Peptides

A sophisticated computer program was designed to filter antimicrobial peptide databases in order to identify specific parameters that could be used to synthesize new and more potent drugs for treatment of infection by methicillin-resistant Staphylococcus aureus (MRSA).

MRSA is any strain of S. aureus that has developed resistance to beta-lactam antibiotics, which include the penicillins and the cephalosporins. The development of such resistance does not cause the organism to be more intrinsically virulent than strains of S. aureus that have no antibiotic resistance, but resistance does make MRSA infection more difficult to treat with standard types of antibiotics and thus more dangerous . MRSA is especially troublesome in hospitals, prisons, schools, and nursing homes, where patients with open wounds, invasive devices, and weakened immune systems are at greater risk of infection than the general public.

Investigators at the University of Nebraska Medical Center (Omaha, USA) recently described their approach for selecting the optimum traits for anti-MRSA peptides by screening databases of antimicrobial peptides for properties such as peptide length, amino acid composition, hydrophobic content, net charge, and three-dimensional structure. Peptides with the desired properties were then synthesized in the laboratory.

Two such peptides were analyzed in a study published in the July 17, 2012, online edition of the Journal of the American Chemical Society. The two peptides, DFTamP1 and temporin-PTa8L were found to rapidly destroy MRSA in culture. Structural determination of DFTamP1 by NMR spectroscopy revealed a broad hydrophobic surface, providing a basis for its potency against MRSA known to deploy positively charged moieties on the surface as a mechanism for resistance.

The authors concluded that, "Because of the simple composition, short length, stability to proteases, and membrane targeting, the designed peptides are attractive leads for developing novel anti-MRSA therapeutics. Our database-derived design concept can be applied to the design of peptide mimicries to combat MRSA as well."

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University of Nebraska Medical Center