Conjugates and compositions for cellular delivery
View Patent ↗This invention features conjugates, compositions, methods of synthesis, and applications thereof, including folate derived conjugates of nucleosides, nucleotides, non-nucleosides, and nucleic acids including enzymatic nucleic acids and antisense nucleic acid molecules.
1. A compound having formula XXV:
wherein each of R 5 and R 7 is independently selected from the group consisting of hydrogen, alkyl and a nitrogen protecting group;
each of R 15 , R 16 , R 17 and R 18 is independently selected from the group consisting of O, S, alkyl, substituted alkyl, aryl, substituted aryl and halogen;
X 1 is —CH(X 1′ ) or a group of formula XXVI:
wherein R 4 is a protecting group and n is an integer from 0 to 200;
X 1′ is a protected or unprotected side chain of a naturally occurring or non-naturally occurring amino acid;
X 2 is selected from the group consisting of amide, alkyl, or carbonyl containing linker and a bond;
and X 3 is a degradable linker which is optionally absent.
2. The compound of claim 1 , wherein each of R 5 and R 7 is independently hydrogen or alkyl.
3. The compound of claim 2 , wherein each of R 5 and R 7 is independently hydrogen or methyl.
4. The compound of claim 1 , wherein each of R 15 , R 16 , R 17 and R 18 is independently selected from the group consisting of O, S, alkyl and substituted alkyl.
5. The compound of claim 4 , wherein each of R 15 , R 16 , R 17 and R 18 is independently selected from the group consisting of O, S and alkyl.
6. The compound of claim 4 , wherein each of R 15 , R 16 , R 17 and R 18 is independently O or S.
7. The compound of claim 1 , wherein X 1 is a group of formula XXVI:
wherein R 4 is a protecting group and n is an integer from 0 to about 200.
8. The compound of claim 1 , wherein X 2 is amide, alkyl, or a bond.
9. The compound of claim 1 , wherein X 3 is a degradable linker.
10. The compound of claim 1 , wherein X 3 is a group of formula XXVI:
wherein R 4 is hydrogen or a protecting group; n is an integer from 0 to about 200; and R 12 is hydrogen, a straight or branched chain alkyl, aryl, or substituted aryl.
11. The compound of claim 10 , wherein R 4 is hydrogen and R 12 is hydrogen or methyl.