2-Aminopropane-1,3-Diol-Capped Cationic Peptoids for Nucleic Acid Delivery
The present disclosure provides delivery vehicle compositions comprising hydroxyalkyl-capped cationic peptoids, such as 2-aminopropane-1,3-diol-capped cationic peptoids, and complexes of the delivery vehicles with polyanionic compounds, such as nucleic acids. The disclosure further provides methods of making and using the delivery vehicle compositions and complexes, such as for the delivery polyanionic compounds (e.g., nucleic acids) to cells. The disclosure also provides methods of eliciting an immune response with the delivery vehicle complexes of the disclosure.
1 . A compound having a structure of Formula (I):
wherein
n is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;
R 1 is H or C 2-5 alkyl optionally substituted with 1-3 OH;
R 2 is C 2-5 alkylene-OH substituted with 1-3 additional OH; and
each R 3 independently is C 6-24 alkyl or C 6-24 alkenyl.
2 . The compound of claim 1 , wherein n is 3, 4, 6, 8, or 9.
3 .- 6 . (canceled)
7 . The compound of claim 1 , wherein R 1 is H.
8 . The compound of claim 1 , wherein R 2 is C 2-5 alkylene-OH substituted with 1 additional OH.
9 . The compound of claim 1 , wherein R 2 is C 2-5 alkylene-OH substituted with 2 or 3 additional OH.
10 . (canceled)
11 . The compound of claim 1 , wherein each R 3 independently is C 6-18 alkyl or C 6-18 alkenyl.
12 . (canceled)
13 . The compound of claim 1 , wherein each R 3 independently is selected from the group consisting of
14 . (canceled)
15 . The compound of claim 1 , wherein at least one R 3 is selected from the group consisting of
16 . (canceled)
17 . The compound of claim 1 , having a structure as recited in Table 1:
TABLE 1
Cmpd
Structure
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
40
41
42
43
44
45
46
47
48
49
51
52
53
54
56
57
58
59
60
61
18 . The compound of claim 17 , having the structure of Compound 1, 6, 12, 21, 30, 34, 35, or 41.
19 .- 25 . (canceled)
26 . A pharmaceutically acceptable salt of the compound of claim 1 .
27 . A delivery vehicle composition comprising the compound of claim 1 .
28 .- 83 . (canceled)
84 . A delivery vehicle complex comprising the delivery vehicle composition of claim 27 , and a polyanionic compound.
85 - 162 . (canceled)
163 . A pharmaceutical composition comprising the delivery vehicle complex of claim 84 , and a pharmaceutically acceptable excipient.
164 . (canceled)
165 . A method of inducing an immune response in a subject in need thereof, comprising administering to the subject an effective amount of the delivery vehicle complex of claim 84 , thereby inducing an immune response in the subject.
166 . A method of treating a viral infection in a subject in need thereof, comprising administering to the subject an effective amount of the delivery vehicle complex of claim 84 , thereby treating the viral infection in the subject.
167 .- 169 . (canceled)
170 . A method of delivering a polyanionic compound to a cell comprising contacting the cell with the delivery vehicle complex of claim 84 .
171 .- 172 . (canceled)
173 . A method of forming the delivery vehicle complex of claim 84 , comprising contacting the compound or salt of Formula (I) with the polyanionic compound.
174 . (canceled)
175 . A vaccine comprising the delivery vehicle complex of claim 84 .
176 . (canceled)
177 . A method of treating or preventing cancer in a patient, comprising administering to the patient the vaccine of claim 175 .
178 . (canceled)