Hybrid SCFA-hydroxyl-derivatized monosaccharides, methods of synthesis, and methods of treating disorders
Described herein are fatty acid carbohydrate-hydroxyl-hybrid compounds and derivatives thereof, and methods of treating or preventing disease and disease symptoms using the compounds and compositions thereof.
1. A compound of formula I, or pharmaceutically acceptable salt thereof:
wherein,
R 4 is H and each of R 1 , R 2 and R 3 is —C(O)(CH 2 ) 2 CH 3 ;
and
R is alkyl, alkenyl or alkyne, each of which is optionally substituted with 1-4 substituents selected from acyl, oxo, azido, aryl, halogen, —OC(O)alkyl, or —SC(O)alkyl.
2. A compound of formula II or formula IV, or a pharmaceutically acceptable salt thereof:
or
wherein,
R 4 is H and each of R 1 , R 2 and R 3 is —C(O)(CH 2 ) 2 CH 3 ; and
R is alkyl, alkenyl or alkyne, each of which is optionally substituted with 1-4 substituents selected from acyl, oxo, azido, aryl, halogen, —OC(O)alkyl, or —SC(O)alkyl.
3. The compound of claim 2 , wherein R is alkyl or a substituted alkyl which may be substituted by oxo, azido, aryl, halogen, —OC(O)alkyl, or —SC(O)alkyl.
4. A compound of formula III, or a pharmaceutically acceptable salt thereof:
wherein,
R 4 is H and each of R 1 , R 2 and R 3 is —C(O)(CH 2 ) 2 CH 3 ; and
R is alkyl, alkenyl or alkyne, each of which is optionally substituted with 1-4 substituents selected from acyl, oxo, azido, aryl, halogen, —OC(O)alkyl, or —SC(O)alkyl.
5. The compound of claim 1 , which comprises mix-match substitution.
6. The compound of claim 1 , wherein the compound is utilized in metabolic labeling of glycoproteins or glycolipids.
7. The compound of claim 1 , wherein the compound is utilized in stem cell differentiation.
8. A method for increasing production of a recombinant glycoprotein in a cell, the method comprising the step of contacting said cell with a compound of formula I, or pharmaceutically acceptable salt thereof:
wherein,
R 4 is H and each of R 1 , R 2 and R 3 is independently —C(O)(CH 2 ) n CH 3 wherein each n is independently an integer from 1-18;
and
R is alkyl, alkenyl or alkyne, each of which is optionally substituted with 1-4 substituents selected from acyl, oxo, azido, aryl, halogen, —OC(O)alkyl, or —SC(O)alkyl,
in an amount sufficient to increase recombinant glycoprotein biosynthesis in said cell, thereby increasing production of a recombinant glycoprotein in said cell.
9. A method of incorporating a compound of formula I, or pharmaceutically acceptable salt thereof:
wherein,
R 4 is H and each of R 1 , R 2 and R 3 is independently —C(O)(CH 2 ) n CH 3 wherein each n is independently an integer from 1-18;
and
R is alkyl, alkenyl or alkyne, each of which is optionally substituted with 1-4 substituents selected from acyl, oxo, azido, aryl, halogen, —OC(O)alkyl, or —SC(O)alkyl,
in a glycan cell surface or in a glycosylation pathway comprising introducing the compound to a recombinant glycoprotein production process, wherein toxicity of said glycoprotein is reduced as compared to an appropriate control.
10. A method of incorporating a compound of formula I, or pharmaceutically acceptable salt thereof:
wherein,
R 4 is H and each of R 1 , R 2 and R 3 is independently —C(O)(CH 2 ) n CH 3 wherein each n is independently an integer from 1-18;
and
R is alkyl, alkenyl or alkyne, each of which is optionally substituted with 1-4 substituents selected from acyl, oxo, azido, aryl, halogen, —OC(O)alkyl, or —SC(O)alkyl,
in a glycan cell surface or in a glycosylation pathway comprising introducing the compound to a recombinant glycoprotein production process, wherein toxicity of said glycoprotein is absent.
11. The compound of claim 1 , wherein R is alkyl, alkenyl or alkyne, each of which is optionally substituted with 1-4 substituents selected from acyl, oxo, azido, aryl, —OC(O)alkyl, or —SC(O)alkyl.
12. The compound of claim 2 , wherein R is alkyl, alkenyl or alkyne, each of which is optionally substituted with 1-4 substituents selected from acyl, oxo, azido, aryl, —OC(O)alkyl, or —SC(O)alkyl.
13. The compound of claim 4 , wherein R is alkyl, alkenyl or alkyne, each of which is optionally substituted with 1-4 substituents selected from acyl, oxo, azido, aryl, —OC(O)alkyl, or —SC(O)alkyl.
14. A method of incorporating a compound of formula I, or pharmaceutically acceptable salt thereof:
wherein,
R 4 is H and each of R 1 , R 2 and R 3 is independently —C(O)(CH 2 ) n CH 3 wherein each n is independently an integer from 1-18;
and
R is alkyl, alkenyl or alkyne, each of which is optionally substituted with 1-4 substituents selected from acyl, oxo, azido, aryl, halogen, —OC(O)alkyl, or —SC(O)alkyl,
in a glycan cell surface or in a glycosylation pathway comprising introducing the compound to a biosynthesis pathway, wherein toxicity is reduced as compared to an appropriate control.
15. A method of incorporating a compound of formula I, or pharmaceutically acceptable salt thereof:
wherein,
R 4 is H and each of R 1 R 2 and R 3 is independently —C(O)(CH 2 ) n CH 3 wherein each n is independently an integer from 1-18;
and
R is alkyl, alkenyl or alkyne, each of which is optionally substituted with 1-4 substituents selected from acyl, oxo, azido, aryl, halogen, —OC(O)alkyl, or —SC(O)alkyl,
in a glycan cell surface or in a glycosylation pathway comprising introducing the compound to a biosynthesis pathway, wherein toxicity is absent.
16. The method of claim 14 , wherein said biosynthesis pathway is selected from the group consisting of a metabolic labeling pathway, a tissue engineering and control of stem cell fate pathway, a pathway for regenerative medicine and a pathway possessing an inborn error of metabolism.
17. The method of claim 15 , wherein said biosynthesis pathway is selected from the group consisting of a metabolic labeling pathway, a tissue engineering and control of stem cell fate pathway, a pathway for regenerative medicine and a pathway possessing an inborn error of metabolism.