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