Surface-immobilized antimicrobial peptoids

Patent metadata

Field	Value
Publication number	US-10676509-B2
Application number	US-53387609-A
Country	US
Kind code	B2
Filing date	Jul 31, 2009
Priority date	Jul 31, 2008
Publication date	Jun 9, 2020
Grant date	Jun 9, 2020

Abstract

Immobilizable antimicrobial compounds incorporating antimicrobial and/or antifouling components, as can be adhered to various device structures and components.

First claim

We claim:

1. An antimicrobial compound comprising
an ampetoid component,
wherein the ampetoid component comprises a trimer of a formula —(—X—Y—Z)— n , wherein X, Y, and Z are independently selected monomeric residues, wherein each monomeric residue is independently selected from proline residues and N-substituted glycine residues,
wherein the N-substituents are independently selected from about C 4 - about C 20 linear, branched and cyclic alkyl moieties, α-amino acid side chain moieties and carbon homologs thereof,

provided the ampetoid component is amphipathic and has a net positive charge under physiological conditions,

an anchor component,
wherein the anchor component comprises at least two DOPA residues and a lysine residue,

an anti-fouling component,
wherein the anti-fouling component comprises at least one N-methoxyethylglycine (N me ) residue,
wherein the anti-fouling component couples the ampetoid component and the anchor component,

wherein the antimicrobial compound comprises a formula
A-(-X—Y—Z—)— n —B—(—N me —) n′ -(-DOPA-Lys-) n″ -DOPA-NH 2

wherein A is selected from H and a terminal N-alkyl substituted glycine residue, N R ,
wherein R is selected from C 4 -C 20 linear, branched and cyclic alkyl moieties,

wherein in the trimer —(—X—Y—Z—)— n , X is selected from an N-(4-(aminobutyl)glycine (N Lys ) residue, at least one of Y and Z is selected from N-(phenylmethyl)glycine (N pm ), (R)—N-(1-phenylethyl)glycine (N gpe ), and (S)—N-(1-phenylethyl)glycine (N spe ) residues, and n is an integer selected from the group consisting of 1-5,

wherein B is selected from a covalent bond, an N Lys residue and N Lys -N spe residues,
wherein n′ is an integer selected from the group consisting of 10-25, and
wherein n″ is an integer selected from the group consisting of 1-5.

2. The compound of claim 1 wherein A is H; and n is 3-4.

3. The compound of claim 2 wherein n is 3; and B is N Lys -N spe residues, said ampetoid component of a formula
H—(—N Lys -N spe —N spe —)—N Lys -N spe .

4. The compound of claim 2 wherein n is 4; and B is selected from a covalent bond and an N Lys residue, said ampetoid component of a formula
H—(—N Lys —N spe —N spe ) 4 or

H—(—N Lys —N spe —N spe —)— 4 N Lys .

5. The compound of claim 1 wherein said ampetoid component is of a formula
H—(—N Lys —N spe —N spe —N Lys —N spe -L-Pro-(-N Lys —N spe —N spe ) 2 .

6. The compound of claim 2 wherein A is a terminal N-alkyl substituted glycine residue, said alkyl substituent R selected from about C 6 to about C 18 linear alkyl moieties; B is a covalent bond; and n is selected from 1 and 2.

7. The compound of claim 2 wherein A is a terminal N-alkyl substituted glycine residue, said alkyl substituent R selected from about C 6 to about C 18 linear, branched and cyclic alkyl moieties; B is an N Lys residue; and n is 1.

8. The compound of claim 7 wherein said ampetoid component is of a formula
H—N tridec —N Lys —N spe —N spe —N Lys .

9. An article of manufacture comprising a metal substrate and a coating coupled thereto, said coating comprising an antimicrobial compound selected from compounds of claim 1 .

10. The article of claim 9 wherein said anchor component comprises a (DOPA-Lys) 2 -DOPA sequence of residues.

11. The article of claim 9 wherein said substrate is a medical device.

12. The article of claim 11 wherein said substrate comprises titanium oxide.

13. An antimicrobial compound of a formula
H—N Lys —N spe —N spe —N Lys —N spe -L-Pro-(N Lys —N spe —N spe ) 2 —(N me ) 20 -(DOPA- Lys ) 2 -DOPA- NH 2 .

Assignees

• Messersmith Phillip B
• Barron Annelise E
• Statz Andrea
• Chongslriwatana Nathaniel
• Univ Northwestern

Inventors

• Messersmith Phillip B
• Barron Annelise E
• Statz Andrea
• Chongslriwatana Nathaniel

Classifications

• C07K14/001

  by chemical synthesis · CPC title

• C09D5/1637

  Macromolecular compounds · CPC title

• C07K7/06

  having 5 to 11 amino acids · CPC title

• B08B17/06

  by giving articles subject to fouling a special shape or arrangement · CPC title

• C09D5/14

  Paints containing biocides, e.g. fungicides, insecticides or pesticides (C09D5/16 takes precedence) · CPC title