Cyclic peptides comprising at least one aza-β3-aminoacyl residue and their uses

1. A cyclic peptide having a random alternation of L-α-aminoacyl residues and aza-β 3 -aminoacyl residues corresponding to formula (A),

wherein,

R1 represents a proteogenic side chain,

providing that,

L-α-aminoacyl residues are always separated by one aza-β 3 -aminoacyl residue, and

the total number of L-α-aminoacyl residues and aza-β 3 -aminoacyl residues is between 4 and 8, inclusive.

2. The cyclic peptide according to claim 1 , wherein the peptide is a hexapeptide or an octapeptide.

3. The cyclic peptide according to claim 1 , wherein the L-α-aminoacyl residues are selected from the group consisting of: arginine, leucine, lysine, phenylalanine, serine, threonine and tryptophan.

4. The cyclic peptide according to claim 1 , wherein R1 represents a side chain of natural amino acid residues or non-natural amino acid residues.

5. The cyclic peptide according to claim 4 , wherein the natural amino acid residues are selected from the group consisting of: arginine, leucine, lysine, phenylalanine, serine, threonine and tryptophan residues.

6. The cyclic peptide according to claim 4 , wherein the non-natural amino acid residues are selected from the group consisting of:

1-naphthylalanine [(1)Nal],

2-naphthylalanine [(2)Nal],

4-phenyl-phenylalanine (4Bip),

diphenylalanine (Dip),

9-anthracenylalanine [(9)Ath],

4-pyridylalanine [(4)Pal],

3-pyridylalanine [(3)Pal],

2-pyridylalanine [(2)Pal],

fluorophenylalanine (4-Fpa),

dodecylalanine (Amy),

nonylalanine (Non),

octylalanine (Oct),

cyclohexylalanine (Cha),

4-fluoro-1-naphthylalanine (4-F-1-Nal),

homoserine (Hse),

homo γ-hydroxythreonine, and

norleucine (Nle) residues.

7. The cyclic peptide according to claim 1 , having the sequence (Ia):

c[azaβ 3 aa 1′ -aa 1 -azaβ 3 aa 2′ -aa 2 -azaβ 3 aa 2′ -aa 3 -(azaβ 3 aa 4′ )m 4 -(aa 4 )n 4 ]  (Ia)

wherein,

each of aa 1 , aa 2 , aa 3 , and aa 4 independently represents an L-α-aminoacyl residue,

each of azaβ 3 aa 1′ , azaβ 3 aa 2′ , azaβ 3 aa 2′ , and azaβ 3 aa 4′ independently represents an aza-β 3 -amino acid, corresponding to formula (A), and

m 4 and n 4 each simultaneously represent 0 or 1.

8. The cyclic peptide according to claim 1 , having the sequence (Ib):

c[aa 1 -azaβ 3 aa 1′ -aa 2 -azaβ 3 aa 2′ -aa 2 -azaβ 3 aa 2′ -(aa 4 )n 4 -(azaβ 3 aa 4′ )m 4 ]  (Ib)

wherein,

each of aa 1 , aa 2 , aa 2 , and aa 4 independently represents an L-α-aminoacyl residue,

each of azaβ 3 aa 4′ , azaβ 3 aa 2′ , azaβ 3 aa 2′ and azaβ 3 aa 4′ , independently represents an aza-β 3 -amino acid, corresponding to formula (A), and

m 4 and n 4 each simultaneously represent 0 or 1.

9. The cyclic peptide according to claim 1 , having the sequence (Ic):

c(azaβ 3 aa 1′ -azaβ 3 aa 2′ -azaβ 3 aa 2′ -aa 1 -azaβ 3 aa 4′ -aa 2 )  (Ic)

wherein,

each of aa 1 and aa 2 independently represents an L-α-aminoacyl residue,

each of azaβ 3 aa 4′ , azaβ 3 aa 2′ , azaβ 3 aa 2′ and azaβ 3 aa 4′ independently represents an aza-β 3 -amino acid, corresponding to formula (A).

10. The cyclic peptide according to claim 1 , having the sequence (Id):

c(azaβ 3 aa 1′ -azaβ 3 aa 2′ -aa 1 -azaβ 3 aa 1′ -aa 2 )  (Id)

wherein,

each of aa 1 and aa 2 independently represents an L-α-aminoacyl residue,

each of azaβ 3 aa 1′ and azaβ 3 aa 2′ independently represents an aza-β 3 -amino acid, corresponding to formula (A).

11. The cyclic peptide according to claim 7 , selected from the group consisting of the following sequences:

SEQ ID NO 1: c[-Leu- azaβ 3 Lys-Lys- azaβ 3 (1)Nal-Leu-

azaβ 3 (1)Nal-] (NafNaf),

SEQ ID NO 2: c[-Lys- azaβ 3 Lys-Leu- azaβ 3 (1)Nal-Leu-

azaβ 3 (1)Nal-] (NalNal),

SEQ ID NO 3: c[-Lys- azaβ 3 Lys-Trp- azaβ 3 Leu-Trp-

azaβ 3 Leu-] (TrypTryp),

SEQ ID NO 4: c[-Lys- azaβ 3 Lys-Lys- azaβ 3 Leu-Trp-

azaβ 3 Leu-] (3KW),

SEQ ID NO 5: c[-Trp- azaβ 3 Lys-Lys- azaβ 3 Lys-Trp-

azaβ 3 Leu-] (3K2),

SEQ ID NO 6: c[-Lys- azaβ 3 Lys-Lys- azaβ 3 Lys-Trp-

azaβ 3 (1)Nal-] (4KW),

SEQ ID NO 7: c[-Ser- azaβ 3 (1)Nal-Phe- azaβ 3 Lys-Thr-

azaβ 3 Lys-Ser- azaβ 3 Lys-] (SNalF),

SEQ ID NO 8: c[Leu- azaβ 3 Arg-Arg- azaβ 3 (1)Nal-Leu-

azaβ 3 (1)Nal-] (RNaf),

SEQ ID NO 9: c[-Leu- azaβ 3 Lys-Lys- azaβ 3 (1)Nal-]

azaβ 3 Leu- azaβ 3 (1)Nal-] (Nafaza)

SEQ ID NO 10: c[-Phe- azaβ 3 Lys-Lys- azaβ 3 (1)Nal-

Phe- azaβ 3 (1)Nal-] (PheNal),

SEQ ID NO 11: c[-Leu- azaβ 3 Lys-Lys- azaβ 3 Leu- azaβ 3

(1)Nal-] (5pNala),

SEQ ID NO 12: c[- azaβ 3 Lys-Lys- azaβ 3 (1)Nal-Leu-

azaβ 3 (1)Nal-] (5pNafa).

SEQ ID NO 13: c[-Leu- azaβ 3 Lys-Lys- azaβ 3 (1)-Nal-

Leu- azaβ 3 (4F-1)Nal-]( 4Fluo1Naf),

SEQ ID NO 14: c[-Lys- azaβ 3 Lys-Trp- azaβ 3 Oct-Trp-

azaβ 3 Oct-] (OctOct),

SEQ ID NO 15: c[-Lys- azaβ 3 Lys-Cha- azaβ 3 Amy-Trp-

azaβ 3 (1)Nal-] (Chado),

SEQ ID NO 16: c[-Arg- azaβ 3 Lys-Cha- azaβ 3 (4)Fpa-Trp-

azaβ 3 Cha-] (FluoKil),

SEQ ID NO 17: c[-Leu- azaβ 3 Lys-Lys- azaβ 3 (2)Nal-Leu-

azaβ 3 (2)Nal-] (Naf2Naf2),

SEQ ID NO 18: c[-Phe- azaβ 3 Lys-Arg- azaβ 3 (2)Nal-Phe-

azaβ 3 (2)Nal-] (PheNar2),

SEQ ID NO 19: c[-Leu- azaβ 3 Lys-Lys- azaβ 3 (1)Nal-Leu-

azaβ 3 (4)Fluo-(1)Nal-] (4FluoNaf),

SEQ ID NO 20: c[-Leu- azaβ 3 Lys-Lys- azaβ 3 Bip-Leu-

azaβ 3 Bip-] (BipBip),

SEQ ID NO 21: c[- azaβ 3 Lys-Lys- azaβ 3 Bip-Leu-

azaβ 3 Bip-] (5pBip),

SEQ ID NO 22: c[-Leu- azaβ 3 Arg-Arg- azaβ 3 (1)Nal-

Leu-] (5pRNaf),

SEQ ID NO 23: c[-Leu- azaβ 3 Lys-Lys-Leu- azaβ 3 (1)

Nal-] (5pNafaza),

SEQ ID NO 24: c[- azaβ 3 Lys-Arg- azaβ 3 (2)Nal-Phe-

azaβ 3 (2)Nal-] (5pPheNar2),

SEQ ID NO 25: c[- azaβ 3 Lys-Lys- azaβ 3 (2)Nal-Leu-

azaβ 3 (2)Nal-] (5pNaf2).

12. A medicament, comprising the cyclic peptide according to claim 1 .

13. The medicament according to claim 12 , wherein the medicament is an anti-infective agent or a disinfectant.

14. A pharmaceutical composition, comprising at least one cyclic peptide according to claim 1 combined with a pharmaceutically acceptable excipient.

15. A method of treating bacterial infections in humans or animals, comprising bringing said bacterial cells into contact with at least one cyclic peptide according to claim 1 , in a quantity of said cyclic peptide sufficient to cause death of the bacterial cells without causing death of cells of said human or said animal.