Sialic acid nucleotide sugars
View Patent ↗The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group to a peptide.
1. A compound having the formula:
wherein
X, Y, Z, A and B are independently selected linking groups which are members selected from O, NR, S and CH 2 ;
wherein
R is a member selected from H, an acetyl group, a water-soluble polymer, and a linker to a water-soluble polymer;
R 1 , R 2 , R 3 , R 4 and R 5 are members independently selected from H, an acetyl group, a poly(alkylene oxide), and a linker joined to a poly(alkylene) oxide;
R 6 is a member selected from H, OH, an acetyl group, and a poly(alkylene oxide); and
i + is a cation,
with the proviso that at least one of R, R 1 , R 2 , R 3 , R 4 , R 5 and R 6 is a member selected from a poly(alkylene oxide), and a linker joined to a poly(alkylene oxide).
2. The compound according to claim 1 , having a formula which is a member selected from:
wherein
R 7 is a member selected from a poly(alkylene oxide) and a linker joined to a poly(alkylene oxide),
i + is a member selected from hydrogen, sodium, potassium, lithium, magnesium, manganese and zinc.
3. A poly(ethylene glycol) molecule having the formula:
wherein
R is a member selected from H, alkyl, aryl, acetal, OHC—, H 2 N—CH 2 CH 2 — and HS—CH 2 CH 2 —;
X, Y and W are members independently selected from O, S, NH and N—R′
wherein
R′ is selected from alkyl and aryl;
m is an integer from 0 to 20;
n is an integer from 1 to 2000;
o is an integer from 0 to 20;
Z is a member selected from (CH 2 ) p U(CH 2 ) s [C(Y′)] r V, (CH 2 ) p C(Y′)V and (CH 2 ) p U(CH 2 ) s C(Y′)V
wherein
U is a member selected from O, S, NH and N—R″
wherein
R″ is selected from alkyl and aryl;
V is a sugar nucleotide;
Y′ is a member selected from O, S, NH and N—R′″
wherein
R′″ is selected from alkyl and aryl;
r is an integer selected from 0 and 1;
p is an integer selected from 0 to 20; and
s is an integer selected from 0 to 20.
4. The poly(ethylene glycol) molecule according to claim 3 , wherein
R is a member selected from H, alkyl, aryl;
X, Y and W are O;
Z is (CH 2 ) p U(CH 2 ) s C(Y′)V
wherein
U is NH; and
Y′ is O.
5. The poly(ethylene glycol) molecule according to claim 3 , where said sugar nucleotide is a member selected from UDP-glycoside, CMP-glycoside, and GDP-glycoside.
6. The poly(ethylene glycol) molecule according to claim 5 , where said sugar nucleotide is a member selected from UDP-galactose, UDP-galactosamine, UDP-glucose, UDP-glucosamine, GDP-mannose, GDP-fucose, CMP-sialic acid, and CMP-NeuAc.
7. A poly(ethylene glycol) molecule having the formula:
wherein
R′ and R″ are members independently selected from H, alkyl, aryl, heteroaryl, NH 2 , CHO, acetal, (CH 2 ) t C(Y′)OH, (CH 2 ) t C(Y′)NH 2 , (CH 2 ) t C(Y′)-halogen-sugar-nucleotide, and protein
wherein
Y′ is a member selected from O, S, NH, N—R i and CH 2 ;
t is an integer from 1 to 20; and
R i is a member selected from alkyl and aryl;
X, Y, W, A and B are members independently selected from O, S, N—R ii and CH 2 ;
wherein
R ii is a member selected from H, alkyl and aryl;
n and p are integers independently selected from 1 to 2000;
m, q, and o are integers independently selected from 0 to 20;
Z is a member selected from (CH 2 ) s U(CH 2 ) v [C(Y′)] r V, (CH 2 ) s C(Y″)V and (CH 2 ) s U(CH 2 ) v C(Y″)V
wherein
U is a member selected from O, S, and N—R ii
wherein
R ii is a member selected from H, alkyl and aryl;
V is a sugar nucleotide;
r is an integer selected from 0 and 1;
s is an integer selected from 0 to 20;
v is an integer selected from 0 to 20; and
Y″ is a member selected from O, S, N—R iii and CH 2
wherein
R iii is a member selected from alkyl and aryl.
8. The poly(ethylene glycol) molecule according to claim 7 , where said sugar nucleotide is a member selected from UDP-glycoside, CMP-glycoside, and GDP-glycoside.
9. The poly(ethylene glycol) molecule according to claim 8 , where said sugar nucleotide is a member selected from UDP-galactose, UDP-galactosamine, UDP-glucose, UDP-glucosamine, GDP-mannose, GDP-fucose, CMP-sialic acid, and CMP-NeuAc.
10. A compound comprising a poly(ethylene glycol) moiety covalently joined to a sugar moiety of a nucleotide sugar.
11. The compound according to claim 10 , wherein said poly(ethylene glycol) moiety and said sugar moiety are covalently joined through a linker moiety.
12. The compound according to claim 11 , where said sugar nucleotide is a member selected from UDP-glycoside, CMP-glycoside, and GDP-glycoside.
13. The compound according to claim 12 , where said sugar nucleotide is a member selected from UDP-galactose, UDP-galactosamine, UDP-glucose, UDP-glucosamine, GDP-mannose, GDP-fucose, CMP-sialic acid, and CMP-NeuAc.
14. The compound according o claim 10 , wherein said poly(ethylene glycol) moiety is a member selected from linear and branched poly(ethylene glycol).
15. The compound according to claim 10 , wherein said poly(ethylene glycol) moiety is monomethoxy-poly(ethylene glycol).
16. The compound according to claim 1 , wherein said poly(alkylene oxide) is a poly(ethylene glycol) and has a molecular weight distribution that is essentially homodisperse.
17. The compound according to claim 16 , wherein said poly(ethylene glycol) is a member selected from linear poly(ethylene glycol) and branched poly(ethylene glycol).
18. The compound according to claim 17 , wherein said poly(ethylene glycol) is monomethoxy-poly(ethylene glycol).
19. The poly(ethylene glycol) molecule according to claim 3 , wherein said poly(ethylene glycol) has a molecular weight distribution that is essentially homodisperse.
20. The poly(ethylene glycol) molecule according to claim 3 , wherein said poly(ethylene glycol) is monomethoxy-poly(ethylene glycol).
21. The poly(ethylene glycol) molecule according to claim 7 , wherein said poly(ethylene glycol) has a molecular weight distribution that is essentially homodisperse.
22. The compound according to claim 10 , wherein said poly(ethylene glycol) has a molecular weight distribution that is essentially homodisperse.
23. The compound according to claim 2 , wherein said compound has a structure according to the following formula:
wherein
R 7 is a member selected from:
i + is Na + .
24. The poly(ethylene glycol) molecule according to claim 3 , wherein
Z is (CH 2 ) p U(CH 2 ) s [C(Y′)] r V; p is 0; s is 0; U is NH and r is a member selected from 0 and 1.
25. The poly(ethylene glycol) molecule according to claim 7 , wherein
Z is (CH 2 ) s U(CH 2 ) v [C(Y′)] r V; s is 0; v is 0; U is NH and r is a member selected from 0 and 1.