Anti-microbial peptides

1. A non-naturally occurring anti-microbial peptide comprising between 5 and 15 natural, synthetic, or chemically modified residues, the peptide comprising the sequence according to Formula I: X 1 -X 2 -X 3 -R 1 -R 2 -[R 3 -R 4 -R 5 -R 6 -R 7 -R 8 -R 9 -R 10 -R 11 -R 12 -R 13 -R 14 -R 15 -R 16 -R 17 ]-Y 1 -Y 2 -Y 3 ,

wherein:

X 1 , X 2 , and X 3 are absent;

R 1 to R 17 represent residues of the anti-microbial peptide, wherein:

R 1 is absent;

R 2 is absent;

R 3 is aspartic acid;

R 4 is Arg or Trp;

R 5 is Arg, Trp, Gln, D-Nal2′, Pro, or His;

R 6 is Arg, Gln, Trp, Tyr, Leu, Nal, D-Nal2′, or Pro;

R 7 is Lys, Trp, Tyr, Leu, Arg, Phe, Nal, or D-Nal2′;

R 8 is absent or is Lys, Trp, Tyr, Leu, Arg, Nal, or D-Nal2′;

R 9 is absent or is Lys, Arg, Tyr, Trp, Leu, or Phe;

R 10 is absent or is Lys, Phe, Trp, Leu, or Arg;

R 11 is absent or is Lys, Leu, Trp, or Arg;

R 12 is absent or is Lys or Trp;

R 13 is absent or is Lys or Trp;

R 14 is absent or is Lys;

R 15 -R 1-7 are absent;

wherein at least one of R 7 to R 14 is Lys, and wherein the peptide is cyclized through a side chain lactam between R 3 and one of the said at least one Lys;

Y 1 , Y 2 , and Y 3 represent optional degradation-resistant C-terminal stabilizing residues; and

wherein an anti-biofilm peptide is covalently linked to the N-terminus of the antimicrobial peptide, the anti-biofilm peptide having the sequence Phe-Arg-Ile-Arg-Val-Arg-Val.

2. The non-naturally occurring anti-microbial peptide of claim 1 , wherein

R 3 is aspartic acid;

R 4 is Arg;

R 5 is Arg;

R 6 is D-Nal2′;

R 7 is Phe;

R 8 is Trp;

R 9 is Arg;

R 10 is Lys; and

R 11 -R 17 are absent.

3. The non-naturally occurring anti-microbial peptide of claim 1 , wherein the anti-biofilm peptide is acylated at the N-terminus.

4. The non-naturally occurring anti-microbial peptide of claim 1 , wherein:

Y 1 and Y 2 are independently selected for each occasion from the group consisting of D -threonine, L -threonine, D -proline, L -proline, β-homo proline, D -alanine, L -alanine, D -valine, L -valine, β-valine, 3-methyl-β-valine, D -leucine, L -leucine, β-leucine, D -norleucine, L -norleucine, D -isoleucine, L -isoleucine, β-isoleucine, D -phenylalanine, L -phenylalanine, or a piperazin-2-one ring; and

Y 3 is absent.

5. The non-naturally occurring anti-microbial peptide of claim 4 , wherein:

Y 1 is D -Val; and

Y 2 is D -Pro.

6. The non-naturally occurring anti-microbial peptide of claim 5 , wherein the C-terminus is amidated.

7. The non-naturally occurring anti-microbial peptide of claim 1 , having the sequence: Ac-Phe-Arg-Ile-Arg-Val-Arg-Val-c[Asp-Arg-Arg-D-Nal(2′)-Phe-Trp-Arg-Lys]- D -Val- D -Pro-CONH 2 .