HODGES, ROBERT S.,CHEN, YUXIN,VASIL, MICHAEL,HANCOCK, ROBERT E. W.,FARMER, SUSAN W.
申请号：
EP05854163
公开号：
EP1838331A4
申请日:
2005.12.15
申请国别(地区):
EP
年份:
2012
代理人:
摘要：
Disclosed herein are novel antimicrobial peptides with useful, improved, or superior properties such as antimicrobial activity, desirable levels of hemolytic activity, and therapeutic index against a broad range of microorganisms including gram-negative and gram-positive bacteria and other organisms having a cellular or structural component of a lipid bilayer membrane. Also provided are methods of making and using such peptides to control microbial growth and in pharmaceutical compositions for treatment or prevention of infections caused by such microorganisms. Certain peptides are disclosed utilizing a structure-based rational design relating to an antimicrobial peptide, V681, with single D-/L-amino acid substitutions or charged residue substitutions in or near the center of the peptide on the nonpolar or polar face. Also disclosed are peptides with one or more amino acids in the D configuration, including peptides with all amino acids in the D configuration. Modified peptide analogs herein can demonstrate one or more properties such as improved antimicrobial activity, specificity, and resistance to degradation. Compositions disclosed herein have useful clinical potential as antibiotics including broad spectrum antibiotics.Linvention concerne de nouveaux peptides antimicrobiens avec des propriétés utiles, améliorées ou supérieures telles quune activité antimicrobienne, des niveaux voulus dactivité hémolytique et un indice thérapeutique contre un large éventail de micro-organismes notamment des bactéries gram négatif et gram positif ainsi que dautres organismes possédant une composante cellulaire ou structurelle dune membrane à double couche lipidique. Linvention concerne également des procédés de fabrication et dutilisation de tels peptides pour maîtriser la croissance microbienne ainsi que dans des compositions pharmaceutiques destinées au traitement ou à la prévention dinfections provoquées par de tels micro-organismes. Certains peptides mettent en oeuvre une con
