β-peptoids with antimicrobial activity

1. A β-peptoid consisting of Formula V:

wherein

n represents the number of repeating units of (A 1 -A i ) and ranges from 1 to 8;

A 1 -A i represent individual monomer units 1 to i,

wherein i is 2 or 3,

(A 1 -A i ) is (A 1 -A 2 ) when i is 2 and (A 1 -A i ) is (A 1 -A 2 -A 3 ) when i is 3, and each individual monomer unit is defined by Formula II:

wherein

R is independently selected from the group consisting of benzyl (Bz), and isobutyl (Ibu), and

R 1 is independently selected from the group consisting of dimethylaminopropyl (DMAP), aminoethyl and aminobutyl;

and wherein the β-peptoid is selected from the group consisting of:

Ac(Bz-DMAP-Ibu) 3 -Lys-NH 2 ;

Ac(Bz-DMAP-Ibu) 5 -Lys-NH 2 ;

Ac(Bz-DMAP-Ibu) 6 -Lys-NH 2 ;

Ac(Bz-Ibu-DMAP) 3 -Lys-NH 2 ;

Ac(Bz-Ibu-DMAP) 4 -Lys-NH 2 ;

Ac(Bz-Ibu-DMAP) 5 -Lys-NH 2 ;

Ac(Ibu-Aminoethyl) 6 -Lys-NH 2 ;

Ac(Ibu-DMAP) 5 -Lys-NH 2 ;

Ac(Ibu-DMAP) 7 -Lys-NH 2 ;

Ac(Ibu-DMAP) 8 -Lys-NH 2 ;

Ac(Ibu-Aminoethyl) 5 -Lys-NH 2 ;

Ac(Ibu-Aminoethyl)- 7 -Lys-NH 2 ;

Ac(Ibu-Aminoethyl) 8 -Lys-NH 2 ;

Ac(Ibu-Ibu-Aminoethyl) 3 -Lys-NH 2 ;

Ac(Ibu-Ibu-Aminoethyl) 4 -Lys-NH 2 ;

Ac(Ibu-Ibu-Aminoethyl) 5 -Lys-NH 2 ;

Ac(Ibu-Ibu-Aminobutyl) 2 -Lys-NH 2 ;

Ac(Ibu-Ibu-Aminobutyl) 3 -Lys-NH 2 ;

Ac(Ibu-Ibu-Aminobutyl) 1 -Lys-NH 2 ;

Ac(Ibu-Aminobutyl) 2 -Lys-NH 2 ; and

Ac(Ibu-Aminobutyl) 3 -Lys-NH 2

Wherein “Ac” is the acetyl group of Formula V and “Lys-NH 2 ” is the lysinamide group of Formula V.

2. An antimicrobial composition comprising at least one β-peptoid according to claim 1 .

3. An antimicrobial substrate comprising at least one β-peptoid according to claim 1 bound to or incorporated into the substrate.

4. An article comprising an antimicrobial substrate of claim 3 wherein the article is selected from the group consisting of a personal care item, an agricultural item, a cosmetic, a package, a food handling item, a food delivery item, a personal garment, a medical device, a personal hygiene item, an article intended for oral contact, a household item, a toy, and a liquid separation article.

5. A method for killing, inhibiting, or preventing the growth of at least one microbe, the method comprising contacting the microbe with an effective amount of the β-peptoid of claim 1 .

6. A method for preparing a β-peptoid according to claim 1 comprising:

i) synthesizing β-peptoid blocks of 2-5 monomers;

ligating the β-peptoid blocks of step (i) by amide bond formation.

7. The method of claim 6 wherein identical β-peptoid blocks are ligated.

8. The method of claim 6 wherein non-identical β-peptoid blocks are ligated.

9. A method for preparing a β-peptoid according to claim 1 comprising:

a) contacting t-butyl acrylate with a primary amine of the Formula R—NH 2 or R 1 —NH 2 , wherein R—NH 2 and R 1 —NH 2 optionally have protecting groups and are defined according to steps (a) and (b) of claim 1 , to form an aminoester;

b) contacting the aminoester of step (a) with acryloyl chloride to form an N-substituted acrylamide;

c) contacting the N-substituted acrylamide of step (b) with a primary amine according to the Formula R—NH 2 or R 1 —NH 2 , wherein R—NH 2 and R 1 —NH 2 optionally have protecting groups and are defined according to steps (a) and (b) of claim 1 , to form an aminoester;

d) repeating steps (b) and (c) 0-4 times to form a β-peptoid oligomer;

e) contacting the terminal secondary amine of the β-peptoid oligomer of step (d) with a protecting group precursor;

f) contacting the β-peptoid oligomer of step (e) with an acid to form a β-peptoid block;

g) optionally contacting a solid phase synthesis resin with a spacer group to form a spacer-derivatized resin;

h) removing the terminal secondary protecting group from the spacer-derivatized resin of step (g);

i) contacting the spacer-derivatized resin of step (h) with a β-peptoid block of step (f) to form a resin-bound β-peptoid intermediate;

j) removing the terminal secondary amine from the resin-bound β-peptoid intermediate of step (i);

k) contacting the resin of step (j) with a second β-peptoid block;

l) repeating steps (j) and (k) 0-25 times until a β-peptoid of desired length is achieved;

m) optionally removing the terminal secondary amine from the β-peptoid of step (l);

n) optionally capping the β-peptoid of step (m);

o) cleaving the β-peptoid of step (n) from the resin; and

p) optionally purifying the cleaved β-peptoid of step (o).

10. A method for preparing an antimicrobial β-peptoid according to claim 1 comprising:

a) contacting resin with acryloyl chloride and triethylamine to form an acrylated resin;

b) contacting the acrylated resin of step (a) with a primary amine of the Formula R—NH 2 or R 1 —NH 2 , wherein R—NH 2 and R 1 —NH 2 optionally have protecting groups and are defined according to steps (a) and (b) of claim 1 ;

c) contacting the product of step (b) with acryloyl chloride and TEA;

d) contacting the product of step (c) with a primary amine of the Formula R—NH 2 or R 1 —NH 2 , wherein R—NH 2 and R 1 —NH 2 optionally have protecting groups and are defined according to steps (a) and (b) of claim 1 ;

e) repeating steps (c) and (d) 0-5 times to form a β-peptoid oligomer;

f) contacting the terminal secondary amine of the β-peptoid oligomer of step (e) with a protecting group precursor;

h) contacting the β-peptoid oligomer of step (f) with an acid to form a β-peptoid block;

g) cleaving the β-peptoid block from the resin;

h) purifying the cleaved β-peptoid block;

i) optionally contacting a solid phase synthesis resin with a spacer group to form a spacer-derivatized resin;

j) removing the terminal secondary amine protecting group from the spacer-derivatized resin of step (i);

k) contacting the spacer-derivatized resin of step (j) with a β-peptoid block of step (h) to form a resin-bound β-peptoid intermediate;

l) removing the terminal secondary amine from the resin-bound β-peptoid intermediate of step (k);

m) contacting the resin of step (l) with a second β-peptoid block;

n) repeating steps (l) and (m) 0-25 times until a β-peptoid of desired length is achieved;

o) optionally removing the terminal secondary amine from the β-peptoid of step (n);

p) optionally capping the p-peptoid of step (o);

q) cleaving the β-peptoid of step (p) from the resin; and

r) optionally purifying the cleaved β-peptoid of step (q).