SHORT FATTY ACID TAIL POLYMYXIN DERIVATIVES AND USES THEREOF

摘要

A method for developing an antibiotic is disclosed. The method comprises thesteps of:a) providing a natural polymyxin or octapeptin compound, or a derivativethereof, havinga total of 4 to 6 positive charges and a terminal moiety (D) comprising atotal of 1 to 5carbon atoms; b) replacing from 1 to 3 residues carrying one or more positivechargeswith a residue not having a positive charge, or with a covalent bond, therebygeneratinga derivative of a polymyxin compound having 3 positive charges and a terminalmoiety(D) comprising a total of 1 to 5 carbon atoms; c) assaying said polymyxinderivative forthe ability to sensitize Gram-negative bacteria to an antibacterial agent; andd) selectingcompounds having the ability to sensitize Gram-negative bacteria to an anti-bacterialagent.