Antibacterial agents comprising conjugates of glycopeptides and peptidic membrane associating elements
AssigneesCambridge University Technical Services Limited, AdProTech Limited
InventorsMatthew Allister Cooper, Jason Richard Betley
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Abstract
The invention concerns agents with anti-bacterial activity and methods and intermediates for their production. The present invention further concerns the use of such agents for the treatment of bacterial infections in animals, including man. The agents are derivatives of vancomycin-type antibiotics, of structure: V-L-W—X; wherein V is a glycopeptide moiety which inhibits peptidoglycan biosynthesis in bacteria; L is a linking group; W is a peptidic membrane-associating element such as an element based on naturally-occurring animal or bacterial peptide antibiotics; and X is hydrogen or a membrane-insertive element.
Claims18
An antibacterial compound of formula V-L-W—X wherein
- V is a glycopeptide moiety which inhibits peptidoglycan
- biosynthesis in bacteria;
- L is a linking group;
- W is a peptidic membrane-associating element;
- and
- X is hydrogen or a membrane-insertive element.
A compound according to any one of the preceding claims wherein V is selected from vancomycin, chloroeremomycin, teicoplanin, A2-2, ristocetin A, eremomycin, balkimycin, actinodin A, complestanin, chloropeptin 1, kistamycin A and avoparcin.
A compound according to any one of the preceding claims wherein W comprises a membrane binding peptide including at least one sequence (Xaa)n, where n is from 1 to 12 and each Xaa is independently lysine or arginine.
A compound according to any one of the preceding claims wherein, W comprises a membrane-binding peptide comprising from 2 to 10 contiguous residues selected from lysine and arginine.
A compound according to any, one of the preceding claims wherein W comprises a membrane-inserting peptide.
A compound according to any one of the preceding claims wherein X is a lipophilic chain which has the following parameters:
- having from 6 to 30 carbon atoms including those of any aromatic rings, if present;
- being straight or branched, and in the case of the latter containing one to three branch points;
- being saturated or unsaturated, in the case of the latter containing one to four double or triple bonds;
- optionally having 1, 2 or 3 heteroatoms (in addition to those, if present, in aromatic rings, if present), independently selected from S, O or N;
- optionally containing one or more, for example two or three, aromatic rings, which may be fused and each of which may contain from 1, 2 or 3 heteroatoms which, if present, are independently selected from N, O or S;
- and
- optionally having from one to three substituents selected from hydroxy, —SH, amino and halo.
Dependencies are inferred from the claim text.