Surfactant peptide nanostructures, and uses thereof
This work describes a new class of short polypeptides that can self-assemble to form regular nanotubes with an average diameters of about 50 nm. These peptides (7 to 8 amino acids) have a structure very similar to those observed in surfactant molecules with a defined hydrophilic head group constituting of charged amino acids and a lipophilic tail made out of hydrophobic amino acids such as alanine, valine or leucine. Cryo-TEM micrographs show numerous three-fold junctions connecting the self-assembling nanostructures and thus leading to the formation of a rather dense network of entangled nanotubes. Additionally, the observation of clear openings at the end of the supramolecular structures confirms the presence of tubular organization.
1. A compound of formula 1:
(φ) m (+) n
1(N-terminus→C-terminus)
wherein: (φ) represents independently for each occurrence a natural D- or L-amino acid comprising a nonpolar and noncharged side chain;
(+) represents independently for each occurrence a natural D- or L-amino acid comprising a side chain that is cationic at physiological pH;
m represents an integer greater than or equal to 5 wherein the upper limit of said integer is less than or equal to 10;
n represents an integer greater than or equal to 1 wherein the upper limit of said integer is less than or equal to 10; and said compound is a surfactant.
2. The compound according to claim 1 , wherein said compound is selected from the group consisting of AAAAAAAAAAHHHHHHHHHH (SEQ ID NO: 52), AAAAAAAAAAKKKKKKKKKK (SEQ ID NO: 55), and AAAAAAAAAARRRRRRRRRR (SEQ ID NO: 57).
3. A compound of formula 2:
(+) n (φ) m
2(N-terminus→C-terminus)
wherein: (φ) represents independently for each occurrence a natural D- or L-amino acid comprising a nonpolar and noncharged side chain;
(+) represents independently for each occurrence a natural D- or L-amino acid comprising a side chain that is cationic at physiological pH;
m represents an integer greater than or equal to 5 wherein the upper limit of said integer is less than or equal to 10;
n represents an integer greater than 1 wherein the upper limit of said integer is less than or equal to 10; and said compound is a surfactant.
4. The compound according to claim 3 , wherein said compound is selected from the group consisting of HHHHHHHHHHAAAAAAAAAA (SEQ ID NO: 53), KKKKKKKKKKAAAAAAAAAA (SEQ ID NO: 54), and RRRRRRRRRRAAAAAAAAAA (SEQ ID NO: 56).
5. The compound of formula 3:
(φ) m (−) n
3(N-terminus→C-terminus)
wherein: (φ) represents independently for each occurrence a natural D- or L-amino acid comprising a nonpolar and noncharged side chain;
(+) represents independently for each occurrence a natural D- or L-amino acid comprising a side chain that is cationic at physiological pH;
m represents an integer greater than or equal to 5 wherein the upper limit of said integer is less than or equal to 10;
n represents an integer greater than 1 wherein the upper limit of said integer is less than or equal to 10; and said compound is a surfactant.
6. The compound according to claim 5 wherein said compound is selected from the group consisting of AAAAAADD (SEQ ID NO: 37), VVVVVVDD, (SEQ E) NO: 38), and LLLLLLDD (SEQ ID NO: 39).
7. A self-assembled nanostructure comprising a compound of claim 6 .
8. The self-assembled nanostructure of claim 7 wherein the self-assembled nanostructure is a nanotube.
9. The compound according to claim 5 , wherein said compound is selected from the group consisting of AAAAAAAAAADDDDDDDDDD (SEQ ID NO: 45), AAAAAAAAAAEEEEEEEEEE (SEQ ID NO: 47), VVVVVVVVVVDDDDDDDDDD (SEQ ID NO: 49), and PPPPPPPPPPDDDDDDDDDD (SEQ ID NO: 51).
10. A compound of formula 4:
(−) n (φ) m
4(N-terminus→C-terminus)
wherein: (φ) represents independently for each occurrence a natural D- or L-amino acid comprising a nonpolar and noncharged side chain;
(+) represents independently for each occurrence a natural D- or L-amino acid comprising a side chain that is cationic at physiological pH;
m represents an integer greater than or equal to 5 wherein the upper limit of said integer is less than or equal to 10;
n represents an integer greater 1 wherein the upper limit of said integer is less than or equal to 10; and said compound is a surfactant.
11. The compound according to claim 10 , wherein said compound is selected from the group consisting of DDDDDDDDDDAAAAAAAAAA (SEQ ID NO: 44), EEEEEEEEEEAAAAAAAAAA (SEQ ID NO: 46), DDDDDDDDDDVVVVVVVVVV (SEQ ID NO: 48), and DDDDDDDDDDPPPPPPPPPP (SEQ ID NO: 50).
12. A compound of formula 5:
(−) n (φ) m (−) n
5(N-terminus→C-terminus)
wherein: (φ) represents independently for each occurrence a natural D- or L-amino acid comprising a nonpolar and noncharged side chain;
(+) represents independently for each occurrence a natural D- or L-amino acid comprising a side chain that is cationic at physiological pH;
m represents an integer greater than or equal to 5 wherein the upper limit of said integer is less than or equal to 10;
n represents an integer greater than 1 wherein the upper limit of said integer is less than or equal to 10; and said compound is a surfactant.
13. The compound according to claim 12 , wherein said compound is selected from the group consisting of DDDDDDDDDDAAAAAAAAAADDDDDDDDDD (SEQ ID NO: 58), EEEEEEEEEEAAAAAAAAAAEEEEEEEEEE (SEQ ID NO: 60), DDDDDDDDDDVVVVVVVVVVDDDDDDDDDD (SEQ ID NO: 62), and DDDDDDDDDDPPPPPPPPPPDDDDDDDDDD (SEQ ID NO: 64).
14. A compound of formula 6:
(+) n (φ) m (+) n
6(N-terminus→C-terminus)
wherein: (φ) represents independently for each occurrence a natural D- or L-amino acid comprising a nonpolar and noncharged side chain;
(+) represents independently for each occurrence a natural D- or L-amino acid comprising a side chain that is cationic at physiological pH;
m represents an integer greater than or equal to 5 wherein the upper limit of said integer is less than or equal to 10;
n represents an integer greater than 1 wherein the upper limit of said integer is less than or equal to 10; and said compound is a surfactant.
15. The compound according to claim 14 , wherein said compound is selected from the group consisting of HHHHHHHHHHAAAAAAAAAAHHHHHHHHHH (SEQ ID NO: 67), KKKKKKKKKKAAAAAAAAAAKKKKKKKKKK (SEQ ID NO: 69), RRRRRRRRRRAAAAAAAAAARRRRRRRRRR (SEQ ID NO: 70).
16. A compound of formula 7:
(φ) m (−) n (φ) m
7(N-terminus→C-terminus)
wherein: (φ) represents independently for each occurrence a natural D- or L-amino acid comprising a nonpolar, noncharged side chain;
(+) represents independently for each occurrence a natural D- or L-amino acid comprising a side chain that is cationic at physiological pH;
m represents an integer greater than or equal to 5 wherein the upper limit of said integer is less than or equal to 10;
n represents an integer greater than 1 wherein the upper limit of said integer is less than or equal to 10; and said compound is a surfactant.
17. The compound according to claim 16 , wherein said compound is selected from the group consisting of AAAAAAAAAADDDDDDDDDDAAAAAAAAAA (SEQ ID NO: 59), AAAAAAAAAAEEEEEEEEEEAAAAAAAAAA (SEQ ID NO: 61), VVVVVVVVVVDDDDDDDDDDVVVVVVVVVV (SEQ ID NO: 63), and PPPPPPPPPPDDDDDDDDDDPPPPPPPPPP (SEQ ID NO: 65).
18. A compound of formula 8:
(φ) m (+) n (φ) m
8(N-terminus→C-terminus)
wherein: (φ) represents independently for each occurrence a natural D- or L-amino acid comprising a nonpolar and noncharged side chain;
(+) represents independently for each occurrence a natural D- or L-amino acid comprising a side chain that is cationic at physiological pH;
m represents an integer greater than or equal to 5 wherein the upper limit of said integer is less than or equal to 10;
n represents an integer greater than 1 wherein the upper limit of said integer is less than or equal to 10; and said compound is a surfactant.
19. The compound according to claim 18 , wherein said compound is selected from the group consisting of AAAAAAAAAAHHHHHHHHHLHAAAAAAAAAA (SEQ ID NO: 66), AAAAAAAAAAKKKKKKKKKKAAAAAAAAAA (SEQ ID NO: 69), and AAAAAAAAAARRRRRRRRRRAAAAAAAAAAA (SEQ ID NO: 71).
20. A compound of formula 9:
(+) n (φ) m (−) n
9(N-terminus→C-terminus)
wherein: (φ) represents independently for each occurrence a natural D- or L-amino acid comprising a nonpolar and noncharged side chain;
(+) represents independently for each occurrence a natural D- or L-amino acid comprising a side chain that is cationic at physiological pH;
m represents an integer greater than or equal to 5 wherein the upper limit of said integer is less than or equal to 10;
n represents an integer greater than 1 wherein the upper limit of said integer is less than or equal to 10; and said compound is a surfactant.
21. The compound according to claim 20 , wherein said compound is selected from the group consisting of KKKKKKKKKKAAAAAAAAAADDDDDDDDDD (SEQ ID NO: 72), KKKKKKKKKKAAAAAAAAAAEEEEEEEEEE (SEQ ID NO: 73), RRRRRRRRRRVVVVVVVVVVDDDDDDDDDD (SEQ ID NO: 74), KKKKKKKKKKPPPPPPPPPPDDDDDDDDDD (SEQ ID NO: 75), and HHHHHHHHHHAAAAAAAAAAEEEEEEEEEE (SEQ ID NO: 76).
22. A compound of formula 10:
(−) n (φ) m (+) n
10(N-terminus→C-terminus)
wherein: (φ) represents independently for each occurrence a natural D- or L-amino acid comprising a nonpolar and noncharged side chain;
(+) represents independently for each occurrence a natural D- or L-amino acid comprising a side chain that is cationic at physiological pH;
m represents an integer greater than or equal to 5 wherein the upper limit of said integer is less than or equal to 10;
n represents an integer greater than 1 wherein the upper limit of said integer is less than or equal to 10; and said compound is a surfactant.
23. A compound of formula 11:
R′(φ) m (−) n CO 2 −
11(N-terminus→C-terminus)
wherein: (φ) represents independently for each occurrence a natural D- or L-amino acid comprising a nonpolar and noncharged side chain;
(+) represents independently for each occurrence a natural D- or L-amino acid comprising a side chain that is cationic at physiological pH;
m represents an integer greater than or equal to 5 wherein the upper limit of said integer is less than or equal to 10;
n represents an integer greater than or equal to 1 wherein the upper limit of said integer is less than or equal to 10; and said compound is a surfactant.
24. The compound of claim 23 wherein R′ is an acetyl group.
25. A self-assembled nanostructure comprising a compound of claim 24 .
26. The self-assembled nanostructure of claim 25 wherein the self-assembled nanostructure is a nanotube.
27. The compound according to claim 24 wherein said compound is selected from the group consisting of AAAAAAD (SEQ ID NO: 35), VVVVVVD (SEQ ID NO: 36), AAAAAADD (SEQ ID NO: 37), VVVVVVDD (SEQ ID NO: 38), and LLLLLLDD (SEQ ID NO: 39).
28. A self-assembled nanostructure comprising a compound of claim 27 .
29. The self-assembled nanostructure of claim 28 wherein the self-assembled nanostructure is a nanotube.
30. The compound according to claim 23 wherein said compound is selected from the group consisting of AAAAAAD (SEQ ID NO: 35), VVVVVVD (SEQ ID NO: 36), AAAAAADD (SEQ ID NO: 37), VVVVVVDD (SEQ ID NO: 38), and LLLLLLDD (SEQ ID NO: 39).
31. A self-assembled nanostructure comprising a compound of claim 30 .
32. The self-assembled nanostructure of claim 31 wherein the self-assembled nanostructure is a nanotube.
33. A self-assembled nanostructure comprising a compound of claim 23 .
34. The self-assembled nanostructure of claim 33 wherein the self-assembled nanostructure is a nanotube.
35. A self-assembled nanostructure comprising a compound of any of claims 2 through 21 .
36. A self-assembled nanostructure, comprising a compound of any of claims 1 through 22 .
37. A surfactant peptide consisting of the amino acid sequence selected from the group consisting of AAAAAAD (SEQ ID NO:35) and VVVVVVD (SEQ ID NO:36).