Cyclization of pyrrhocoricin retains structural elements crucial for the antimicrobial activity of the native peptide.
Pyrrhocoricin is a naturally occurring antimicrobial peptide from the European fire bug Pyrrhocoris apterus. It has submicromolar activity against a range of Gram-negative bacterial strains and has created recent interest as a lead for the development of novel antibiotic compounds. In this study, we have used NMR spectroscopy to determine the solution structures of pyrrhocoricin and a synthetic macrocyclic derivative that has improved in vivo pharmaceutical properties. Native pyrrhocoricin is largely disordered in solution, but there is evidence of a subpopulation with ordered turn regions over residues 2-5, 4-7, and 16-19. The macrocyclic derivative incorporates a nine amino acid linker joining the N- and C-termini, which does not adversely affect the antimicrobial potency but leads to a broader spectrum of activity. The NMR data suggest that the turn conformations in the cyclic derivative are similar to those in the native form, thus implicating them in the biological function.
Rosengren
K Johan
KJ
Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia.
Göransson
Ulf
U
Otvos
Laszlo
L
Craik
David J
DJ
D000596:Amino Acids / Q000235:genetics / Q000378:metabolism; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects*; D019476:Insect Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D007313:Insecta; D009682:Magnetic Resonance Spectroscopy; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
D000596:Amino Acids; D023181:Antimicrobial Cationic Peptides; D019476:Insect Proteins; D010456:Peptides, Cyclic; C087710:pyrrhocoricin protein, Pyrrhocoris apterus