Chemical synthesis and biological evaluation of an antimicrobial peptide gonococcal growth inhibitor |
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Authors: | John D Wade Feng Lin Mohammed Akhter Hossain Raymond M Dawson |
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Institution: | 1. Florey Neuroscience Institutes, University of Melbourne, Melbourne, VIC, 3010, Australia 2. School of Chemistry, University of Melbourne, Melbourne, VIC, 3010, Australia 3. Defence Science and Technology Organisation, 506 Lorimer Street, Fishermans Bend, Melbourne, VIC, 3207, Australia
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Abstract: | Gonococcal growth inhibitor 1 (GGI-1) is a 44-residue peptide with potent anti-Legionella activity. It has been isolated from Staphylococcus haemolyticus but, to date, its chemical synthesis has not been reported. Acquisition of this peptide via this means would enable a more detailed examination of its antimicrobial properties. However, its synthesis represents a significant challenge because of two predicted “difficult sequences” within the peptide. Its successful solid-phase assembly is reported in this paper, and was accomplished by use of simple palliative measures including the introduction of a single pseudo-proline isostere in order to counteract on-resin aggregation. The peptide had moderate antimicrobial activity against Escherichia coli but was inactive against another Gram-negative bacterium and two Gram-positive bacteria (Bacillus species). It had significant haemolytic activity, with a H50 (concentration of peptide that causes 50?% haemolysis) of 20 and 125?μM for two blood samples from different donors. An alternative therapeutic index to that proposed for GGI-1 in a recent publication is proposed. |
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