Patent ID: 9067974
Filing Date: 2015-06-30
Classification: A61K,A61P,C07K,C12Q,Y02A

Abstract:
1. A method for developing antibiotics comprising the steps of a) providing a natural polymyxin or octapeptin compound, or a derivative thereof, having a total of 4 to 6 positive charges, and having an amino acid residue present in the positions equivalent to R2 and R3 of polymyxin B; b) substituting from 1 to 4 residues carrying one or more positive charges with a residue not having a positive charge, or with a covalent bond, thereby generating a derivative of a polymyxin compound having 2 or 3 positive charges, and having an amino acid residue present in the positions equivalent to R2 and R3 of polymyxin B, with the proviso that R8 and R9 are not both formylated when R(FA)-R1-R2-R3 constitutes the native polymyxin B side chain, and with the proviso that the derivative is not di-N-acetylated- or tri-N-acetylated-polymyxin B; c) assaying said derivative compound for antibacterial activity against Gram-negative bacteria; or the ability to sensitize Gram-negative bacteria to an antibacterial agent; and d) selecting compounds having antibacterial activity against Gram-negative bacteria, or the ability to sensitize Gram-negative bacteria to the antibacterial agent.