Antimicrobial compounds and formulations
View Patent ↗The invention relates to the use of a molecule comprising a backbone of 2 to 35 non-hydrogen atoms in length, having covalently attached thereto at least two bulky and lipophilic groups and having at least one more cationic than anionic moiety, in the manufacture of a medicament for destabilizing microbial cell membranes and the use as a membrane acting antimicrobial agent of a molecule comprising a backbone of 2 to 35 non-hydrogen atoms in length, having covalently attached thereto a super bulky and lipophilic group comprising at least 9 non-hydrogen atoms and having at least two more cationic than anionic moieties and to methods of treatment involving such molecules, in particular peptides including peptide derivatives, and peptidomimetics.
1. A method of destabilizing microbial cell membranes in a patient suffering from or at risk of being affected by a microbial infection which comprises administering to said patient a molecule of 2 to 4 amino acids or equivalent subunits in length, and incorporating a bulky and lipophilic group comprising at least 11 non-hydrogen atoms and containing no more than 2 polar functional groups, wherein said bulky and lipophilic group incorporates one or more closed rings of 5 or more non-hydrogen atoms, said molecule further having at least two more cationic than anionic moieties.
2. A method as claimed in claim 1 , wherein said bulky and lipophilic group comprises at least 13 non-hydrogen atoms.
3. A method as claimed in claim 1 , wherein said super bulky group incorporates 2 closed rings of 5 or more non-hydrogen atoms.
4. A method as claimed in claim 1 wherein said molecule is a peptide, peptide derivative or peptidomimetic.
5. A method as claimed in claim 4 , wherein said molecule comprises a modified C terminus which does not carry a negative charge.
6. A method as claimed in claim 5 , wherein said C terminus is amidated or esterified.
7. A method as claimed in claim 5 or 6 , wherein said modified C terminus comprises a bulky and lipophilic group.
8. A method as claimed in claim 4 wherein said peptide, peptide derivative or peptidomimetic comprises one or more amino acid or equivalent R subunits which comprises a bulky and lipophilic group.
9. A method as claimed in claim 8 , wherein one or more of said amino acid or subunits comprises a cationic moiety.