Peptoids and methods for treating Alzheimer's disease
Provided herein are peptoids capable of inhibiting or reversing amyloid β (Aβ) fibril or plaque production. The peptoids form a helical structure with three monomers per helical turn and have at least four monomers with a side-chain having an arylalkyl or aryl group. The peptoid may be achiral. Also provided are methods of using the peptoids to inhibit or reverse aggregation of Aβ and methods of treating subjects with Alzheimer's disease (AD) or slowing the progression of AD.
1. A peptoid composition comprising eight peptoid monomers,
wherein the eight peptoid monomers are arranged in consecutive order from the N-terminal end to the C-terminal end and comprise achiral side chain groups R 1 , R 2 , R 3 , A 1 , A 2 , X, A 3 , and A 4 , respectively,
wherein R 1 is selected from an unbranched, terminally substituted C 2 -C 5 aminoalkyl group,
wherein each of R 2 and R 3 of the peptoid is independently selected from an unbranched, unsubstituted C 1 -C 5 alkyl group;
wherein each of A 1 , A 2 , A 3 , and A 4 of the peptoid are independently selected from a C 6 aryl or an unbranched C 7 -C 8 arylalkyl group,
wherein X of the peptoid is an unbranched, unsubstituted C 1 -C 5 alkyl group.
2. The peptoid of claim 1 , wherein each of A 1 , A 2 , A 3 , and A 4 are a phenylmethyl group.
3. The peptoid of claim 1 , wherein R 1 is a 4-aminobutyl group.
4. The peptoid of claim 1 , wherein R 2 and R 3 are propyl groups.
5. The peptoid of claim 1 , wherein X is a propyl group.
6. A pharmaceutical composition comprising the peptoid of claim 1 and a pharmaceutically acceptable carrier.
7. The peptoid of claim 1 , wherein each of A 1 , A 2 , A 3 , and A 4 are a phenylmethyl group and R 2 , R 3 , and X are propyl groups.
8. The peptoid of claim 1 , wherein R 1 is a 4-aminobutyl group and each of A 1 , A 2 , A 3 , and A 4 are a phenylmethyl group.
9. The peptoid of claim 1 , wherein R 1 is a 4-aminobutyl group and R 2, R 3 , and X are propyl groups.
10. A peptoid of formula
11. A pharmaceutical composition comprising the peptoid of claim 10 and a pharmaceutically acceptable carrier.
12. The peptoid of claim 10 , wherein the peptoid is part of a longer peptoid chain.
13. A pharmaceutical composition comprising the peptoid of claim 12 and a pharmaceutically acceptable carrier.