Back to Search Start Over

nNOS inhibition, antimicrobial and anticancer activity of the amphibian skin peptide, citropin 1.1 and synthetic modifications. The solution structure of a modified citropin 1.1.

Authors :
Doyle J
Brinkworth CS
Wegener KL
Carver JA
Llewellyn LE
Olver IN
Bowie JH
Wabnitz PA
Tyler MJ
Source :
European journal of biochemistry [Eur J Biochem] 2003 Mar; Vol. 270 (6), pp. 1141-53.
Publication Year :
2003

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 alpha-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 alpha-helix.

Details

Language :
English
ISSN :
0014-2956
Volume :
270
Issue :
6
Database :
MEDLINE
Journal :
European journal of biochemistry
Publication Type :
Academic Journal
Accession number :
12631273
Full Text :
https://doi.org/10.1046/j.1432-1033.2003.03462.x