Immunomodulating beta-1,6-D-glucans
This invention relates to modifications of β-1,6-D-glucans, e.g., structures according to Formula (I), and the ability of these compositions to modulate an immune response.
1. A compound having a structure according to the following general formula (I),
wherein
n is an integer from 1 to 18;
B is —CH 2 OH, —CHO, or —CO 2 H;
A is α and is:
(a) —OR, wherein R is alkenyl, alkynyl, aryl, heteroaryl, or heteroaliphatic;
(b) —SR, wherein R is alkyl, alkenyl, alkynyl, aryl, heteroaryl, or heteroaliphatic;
(c)a 6-O-substituted-D-glucosamine (W),
wherein
R′ is alkyl, aryl, or heteroaryl;
(d)a 6-O-substituted-C-glycoside (X),
wherein
R 1 is H; and R 2 is alkenyl, alkynyl, or heteroaliphatic; or
R 2 is H; and R 1 is alkenyl, alkynyl, or heteroaliphatic;
and
a is 0, 1, 2, 3, 4, or 5
wherein
R is H, alkyl, or aryl, and
azidoalkvl is an alkyl group comprising an azide moiety;
wherein
A′ is alkyl, aryl, or heteroaryl; A″ is carboxy alkyl, carboxy aryl, or carboxy heteroaryl; carboxy alkyl represents a residue formed from an aliphatic amino acid; carboxy aryl represents a residue formed from an aromatic amino acid; and carboxy heteroaryl represents a residue formed from a heteroaromatic amino acid;
wherein
A′ is alkyl, aryl, or heteroaryl; and aminoalkyl represents an alkyl group containing an amino moiety;
or
2. The compound of claim 1 , wherein group A is —SR.
3. The compound of claim 1 , wherein group A is —O(CH 2 CH 2 O)aCH 2 CH 2 N 3, wherein a is 0, 1, 2, 3, 4, or 5.
4. The compound of claim 1 , wherein group A is a 6-O-substituted-D-glucosamine (W),
5. The compound of claim 1 , wherein group A is
wherein R is H, alkyl, or aryl, and azidoalkyl is an alkyl group containing an azide moiety.
6. The compound of claim 5 , wherein R is unsubstituted alkyl or substituted alkyl.
7. The compound of claim 1 , wherein group A is
8. The compound of claim 7 , wherein A′ is alkyl or aryl; and
A″ is carboxy alkyl.
9. The compound of claim 1 , wherein group A is
10. The compound of claim 1 , wherein said compound has a structure according to formula (Ib),
wherein
n is an integer between 1-18, and
R is selected from alkyl, alkenyl, alkynyl, alkylene, alkynylene, aryl, and heteroaryl.
11. A compound having a structure according to formula (Ic)
wherein n is an integer between 1-18, and
R is alkyl.
12. A compound having a structure according to formula (Id),
wherein n is an integer between 1-18, and
R is alkyl.
13. A compound having a structure according to the following general formula (I),
wherein
n is an integer from 1 to 18;
B is —CH 2 OH, —CHO, or —CO 2 H;
A is:
(a) —SR, wherein R is alkyl, alkenyl, alkynyl, aryl, heteroaryl, or heteroaliphatic;
(b) —O(CH 2 CH 2 O)aCH 2 CH 2 N 3, wherein a is 0, 1, 2, 3, 4, or 5;
(c) a 6-O-substituted-D-glucosamine (W),
wherein
R′ is alkyl, aryl, or heteroaryl;
wherein
R is H, alkyl, or aryl, and
azidoalkyl is an alkyl group comprising an azide moiety;
wherein
A′ is alkyl, aryl, or heteroaryl; A″ is carboxy alkyl, carboxy aryl, or carboxy heteroaryl; carboxy alkyl represents a residue formed from an aliphatic amino acid; carboxy aryl represents a residue formed from an aromatic amino acid; and carboxy heteroaryl represents a residue formed from a heteroaromatic amino acid;
wherein
A′ is alkyl, aryl, or heteroaryl; and aminoalkyl represents an alkyl group containing an amino moiety; or
(g) —O -alkyl, when B is —CHO, or —CO 2 H.
14. The compound of claim 13 , wherein A is β.
15. The compound of claim 13 , wherein group A is
wherein R is H, alkyl, or aryl, and azidoalkyl is an alkyl group containing an azide moiety.
16. The compound of claim 15 , wherein R is unsubstituted alkyl or substituted alkyl.
17. The compound of claim 13 , wherein group A is
18. The compound of claim 17 , wherein:
A′ is alkyl or aryl; and
A″ is carboxy alkyl.
19. The compound of claim 13 , wherein group A is