title: Chemical synthesis and biological evaluation of an antimicrobial peptide gonococcal growth inhibitor.
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 H(50) (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.
authors.affiliation: Florey Neuroscience Institutes, University of Melbourne, Melbourne, VIC, 3010, Australia. john.wade@florey.edu.au
authors.forename: John D
authors.initials: JD
authors.lastname: Wade
authors.forename: Feng
authors.initials: F
authors.lastname: Lin
authors.forename: Mohammed Akhter
authors.initials: MA
authors.lastname: Hossain
authors.forename: Raymond M
authors.initials: RM
authors.lastname: Dawson
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D001426:Bacterial Proteins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; C043217:gonococcal growth inhibitor protein, Staphylococcus haemolyticus