Antimicrobial peptides and their use for the treatment of topical infections

Patent metadata

Field	Value
Publication number	US-10160785-B2
Application number	US-201615564035-A
Country	US
Kind code	B2
Filing date	Apr 8, 2016
Priority date	Apr 10, 2015
Publication date	Dec 25, 2018
Grant date	Dec 25, 2018

Abstract

Synthetic analogs of general formula (I-A),
(I-A) a -Ile- b - c - d - e - f -Lys-Lys- g - h - i - j -Ile- k -Lys-NH 2
where a is Gly, Lys or β-Ala; b is Met, Leu, Nle, Ile, Trp, Val or Phe; c is Ser, Lys, Arg or Orn; d is Ser, Lys, Arg or Orn; e is Leu, Nle, Ile, Trp, Val or Phe; f is Met, Leu, Nle, Ile, Trp, Val or Phe; g is Leu, Nle, Ile or Trp; h is Lys, Arg, Orn or Ala; i is Lys, Arg, Orn or Ala; j is Ile, Leu, Nle or His; k is Lys, Arg, Orn or Ala; where amino acids in all positions may be in D-configuration, and their use for the treatment of topical infections caused by pathogenic bacteria or yeasts.

First claim

The invention claimed is:

1. An antimicrobial peptide selected from the group consisting of formulae I to XIX:

(I)

(SEQ ID NO. 3)

H-Gly-Ile-Met-Ser-Ser-Leu-Met-Lys-Lys-Leu-Lys-Lys-

Ile-Ile-Ala-Lys-NH 2 ,

(II),

(SEQ ID NO. 4)

H- Gly-Ile-Met-Ser-Ser-Leu-Met-Lys-Lys-Leu-Lys-Lys -

Ile-Ile-Ala-Lys -NH 2 ,

(III),

(SEQ ID NO. 5)

H-Gly-Ile-Leu-Ser-Ser-Leu-Leu-Lys-Lys-Leu-Lys-Lys-

Ile-Ile-Ala-Lys-NH 2 ,

(IV),

(SEQ ID NO. 6)

H- Gly-Ile-Leu-Ser-Ser-Leu-Leu-Lys-Lys-Leu-Lys-Lys -

Ile-Ile-Ala-Lys -NH 2 ,

(V),

(SEQ ID NO. 7)

H-Gly-Ile-Nle-Ser-Ser-Leu-Nle-Lys-Lys-Leu-Lys-Lys-

Ile-Ile-Ala-Lys-NH 2 ,

(VI),

(SEQ ID NO. 8)

H- Lys -Ile-Leu-Ser-Ser-Leu-Leu-Lys-Lys-Leu-Lys-Lys-

Ile-Ile-Ala-Lys-NH 2 ,

(VII),

(SEQ ID NO. 9)

H-Gly-Ile-Met-Ser-Ser-Leu-Met-Lys-Lys-Leu-Lys-Lys-

Ile-Ile-Lys-Lys-NH 2 ,

(VIII),

(SEQ ID NO. 10)

H-Gly-Ile-Met-Ser-Ser-Leu-Met-Lys-Lys-Leu-Ala-Ala-

His-Ile-Lys-Lys-NH 2 ,

(IX),

(SEQ ID NO. 11)

H-Gly-Ile-Met-Ser-Ser-Leu-Met-Lys-Lys-Leu-Ala-Ala-

Ile-Ile-Lys-Lys-NH 2 ,

(X),

(SEQ ID NO. 12)

H-Gly-Ile-Leu-Lys-Ser-Leu-Leu-Lys-Lys-Leu-Lys-Lys-

Ile-Ile-Ala-Lys-NH 2 ,

(XI),

(SEQ ID NO. 13)

H-Gly-Ile-Leu-Ser-Lys-Leu-Leu-Lys-Lys-Leu-Lys-Lys-

Ile-Ile-Ala-Lys-NH 2 ,

(XII),

(SEQ ID NO. 14)

H-Gly-Ile-Leu-Ser-Ser-Leu-Trp-Lys-Lys-Leu-Lys-Lys-

Ile-Ile-Ala-Lys-NH 2 ,

(XIII),

(SEQ ID NO. 15)

H- Gly-Ile-Leu-Ser-Ser-Leu-Trp-Lys-Lys-Leu-Lys-Lys -

Ile-Ile-Ala-Lys -NH 2 ,

(XIV),

(SEQ ID NO. 16)

H-Gly-Ile-Trp-Ser-Ser-Leu-Leu-Lys-Lys-Leu-Lys-Lys-

Ile-Ile-Ala-Lys-NH 2 ,

(XV),

(SEQ ID NO. 17)

H-Gly-Ile-Leu-Ser-Ser-Trp-Leu-Lys-Lys-Leu-Lys-Lys-

Ile-Ile-Ala-Lys-NH 2 ,

(XVI),

(SEQ ID NO. 18)

H-Gly-Ile-Leu-Ser-Ser-Leu-Leu-Lys-Lys-Trp-Lys-Lys-

Ile-Ile-Ala-Lys-NH 2 ,

(XVII),

(SEQ ID NO. 19)

H-Gly-Ile-Leu-Ser-Ser-Leu-Trp-Lys-Lys-Leu-Lys-Lys-

Trp-Ile-Ala-Lys-NH 2 ,

(XVIII),

(SEQ ID NO. 20)

H-Gly-Ile-Leu-Ser-Ser-Leu-Leu-Lys-Lys-Leu-Lys-Lys-

Trp-Ile-Ala-Lys-NH 2 ,

and

(XIX),

(SEQ ID NO. 21)

H-Gly-Ile-Leu-Ser-Ser-Leu-Trp-Lys-Lys-Leu-Lys-Lys-

Ile-Ile-Ala- Lys -NH 2 ,

where amino acids in the D configuration are shown in italics.

2. A pharmaceutical composition for use in the treatment or prevention of a topical infection comprising a therapeutically effective amount of at least one of the peptides of formulae I to XIX of claim 1 , wherein the topical infection is selected from the group consisting of difficult-to-heal wounds and skin disorders, mucosal infections, infectious diseases of bone and surrounding tissues, and infections that are caused by the formation of microbial biofilms.

3. A pharmaceutical composition for use in the

Assignees

• Ustav Organicke Chemie A Biochemie Av Cr V V I
• Fyziologicky Ustav Av Cr V V I

Inventors

• Cerovsky Vaclav
• Nesuta Ondrej
• Dudkova Vlasta
• Sychrova Hana
• Kodedova Marie

Classifications

• A61P31/10

  Antimycotics · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• A61P19/00

  Drugs for skeletal disorders · CPC title