nNOS inhibition, antimicrobial and anticancer activity of the amphibian skin peptide, citropin 1.1 and synthetic modifications
Date
2003
Authors
Doyle, J.
Brinkworth, C.
Wegener, K.
Carver, J.
Llewellyn, L.
Olver, I.
Bowie, J.
Wabnitz, P.
Tyler, M.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
The Federation of European Biochemical Societies (FEBS) Journal, 2003; 270(6):1141-1153
Statement of Responsibility
Jason Doyle, Craig S. Brinkworth, Kate L. Wegener, John A. Carver, Lyndon E. Llewellyn, Ian N. Olver, John H. Bowie, Paul A. Wabnitz, Michael J. Tyler
Conference Name
Abstract
A large number of bioactive peptides have been isolated from amphibian skin secretions. These peptides have a variety of actions including antibiotic and anticancer activities and the inhibition of neuronal nitric oxide synthase. We have investigated the structure–activity relationship of citropin 1.1, a broad-spectrum antibiotic and anticancer agent that also causes inhibition of neuronal nitric oxide synthase, by making a number of synthetically modified analogues. Citropin 1.1 has been shown previously to form an amphipathic α-helix in aqueous trifluoroethanol. The results of the structure–activity studies indicate the terminal residues are important for bacterial activity and increasing the overall positive charge, while maintaining an amphipathic distribution of residues, increases activity against Gram-negative organisms. Anticancer activity generally mirrors antibiotic activity suggesting a common mechanism of action. The N-terminal residues are important for inhibition of neuronal nitric oxide synthase, as is an overall positive charge greater than three. The structure of one of the more active synthetic modifications (A4K14-citropin 1.1) was determined in aqueous trifluoroethanol, showing that this peptide also forms an amphipathic α-helix.
School/Discipline
Dissertation Note
Provenance
Published Online: 19 Feb 2003
Description
The definitive version is available at www.blackwell-synergy.com