Modified glycolipids and methods of making and using the same

1. A method of treating a disease in a subject, comprising administering to a subject in need of said treatment a modified glycolipid/protein complex comprising:

a) a CD1d protein;

b) a β2-microglobulin physically associated with said CD1d protein; and

c) a modified α-glycosyl ceramide;

wherein the disease is a viral disease; wherein the modified α-glycosyl ceramide is covalently linked to the CD1d protein via activation of a benzophenone group attached to the terminus of an acyl chain of the N-acyl lipophilic moiety of the modified α-glycosyl ceramide, wherein the modified glycolipid/protein complex enhances the activity of natural killer T (NKT) cells, and wherein the modified glycolipid/protein complex is administered in an amount sufficient to alter the progression of the disease.

2. The method of claim 1 , wherein the viral disease is hepatitis (HAV, HBV, or HCV), or HIV infection.

3. The method of claim 1 , wherein the acyl chain is selected from the group consisting of:

wherein Y is —O—, —CH 2 —, —S—, —OCH 2 —, —SCH 2 —, —CH 2 CH 2 —, or a bond; and PRG is the photoreactive group.

4. The method of claim 1 , wherein said α-galactosylceramide or analog thereof comprises Formula II:

wherein

R1 is a linear or branched C 1 -C 27 alkane or C 2 -C 27 alkene; or R1 is —C(OH)—R3 wherein

R3 is linear or branched C 1 -C 26 alkane or C 2 -C 26 alkene; and

R2 is one of the following (a)-(e):

(a) —CH 2 (CH 2 ) x CH 3 ,

(b) —CH(OH)(CH 2 ) x CH 3 ,

(c) —CH(OH)(CH 2 ) x CH(CH 3 ) 2 ,

(d) —CH═CH(CH 2 ) x CH 3 ,

(e) —CH(OH)(CH 2 ) x CH(CH 3 )CH 2 CH 3 ,

wherein X is an integer ranging from 4-17.

5. The method of claim 4 , wherein R2 is —CH(OH)—(CH 2 ) 13 CH 3 .

6. The method of claim 4 , wherein R1 is selected from the group consisting of (CH 2 ) 9 CH═CH—CH 2 —CH═CH(CH 2 ) 4 CH 3 , (CH 2 ) 8 CH═CH—CH 2 —CH═CH(CH 2 ) 4 CH 3 , (CH 2 ) 7 CH═CH—CH 2 —CH═CH(CH 2 ) 4 CH 3 , (CH 2 ) 3 CH═CH—CH 2 —CH═CH—CH 2 —CH═CH—CH 2 —CH═CH—(CH 2 ) 4 CH 3 , (CH 2 ) 3 CH═CH—CH 2 —CH═CH—CH 2 —CH═CH—CH 2 —CH═CH—CH 2 —CH═CH—CH 2 CH 3 , (CH 2 ) 7 CH═CH—CH 2 —CH═CH═(CH 2 ) 4 CH 3 , (CH 2 ) 7 CH═CH—CH═CH(CH 2 ) 5 CH 3 , (CH 2 ) 8 CH═CH—CH═CH(CH 2 ) 4 CH 3 , (CH 2 ) 9 CH═CH—CH═CH(CH 2 ) 5 CH 3 , (CH 2 ) 6 CH═CH—CH═CH—CH═CH(CH 2 ) 4 CH 3 and (CH 2 ) 7 CH═CH—CH═CH—CH═CH(CH 2 ) 3 CH 3 .

7. The method of claim 1 , wherein said α-galactosylceramide or analog thereof comprises Formula III:

wherein R is —C(O)R1, wherein R1 is a linear or branched C 1 -C 27 alkane or C 2 -C 27 alkene; or R1 is —C(OH)—R3 wherein R3 is a linear or branched C 1 -C 26 alkane or C 2 -C 26 alkene; or R1 is a C 6 -C 27 alkane or alkene wherein (i) the C 6 -C 27 alkane or alkene is substituted with a C 5 -C 15 cycloalkane, C 5 -C 15 cycloalkene, heterocycle, or aromatic ring or (ii) the C 6 -C 27 alkane or alkene includes, within the C 6 -C 27 alkyl or alkenyl chain, a C 5 -C 15 cycloalkane, C 5 -C 15 cycloalkene, heterocycle, or aromatic ring; or R1 is an optionally substituted aromatic ring, or an aralkyl, and

R2 is one of the following (a)-(e):

(a) —CH 2 (CH 2 ) x CH 3 ,

(b) —CH(OH)(CH 2 ) x CH 3 ,

(c) —CH(OH)(CH 2 ) x CH(CH 3 ) 2 ,

(d) —CH═CH(CH 2 ) x CH 3 ,

(e) —CH(OH)(CH 2 ) x CH(CH 3 )CH 2 CH 3 ,

wherein X is an integer ranging from 4-17.

8. The method of claim 1 , wherein said α-galactosylceramide or analog thereof is selected from the group consisting of: (2S, 3S, 4R)-1-O-(α-D-galactopyranosyl)-N-hexacosanoyl-2-amino-1,3,4-octadecanetriol (KRN7000), (2S,3S)-1-O-(α-D-galactopyranosyl)-N-hexacosanoyl-2-amino-1,3-octadecanediol), and (2S, 3S, 4R)-1-CH 2 -(α-galactopyranosyl)-N-hexacosanoyl-2-amino-1,3,4-octadecanetriol (α-C-GalCer).

9. The method of claim 1 , wherein the modified α-galactosylceramide has a structure selected from the group consisting of: