Content dependent inhibitors of cytidine deaminases and uses thereof

1. A context-dependent cytidine deaminase inhibitor comprising a nucleoside incorporated in a polymeric substrate, wherein the polymeric substrate selectively targets a cytidine deaminase, further wherein the polymeric substrate comprises a mooring sequence.

2. The context-dependent cytidine deaminase inhibitor of claim 1 , wherein the nucleoside comprises a base, wherein the base of the nucleoside is susceptible to nucleophilic attack.

3. The context-dependent cytidine deaminase inhibitor of claim 1 , wherein the nucleoside comprises a base, wherein the base of the nucleoside comprises a sp2 carbon center susceptible to nucleophilic attack.

4. The context-dependent cytidine deaminase inhibitor of claim 3 , wherein an electrophilic group is present at the sp2 carbon center.

5. The context-dependent cytidine deaminase inhibitor of claim 3 , wherein the Sp2 carbon center is a carbonyl group, an imino group, or an alkenyl group.

6. The context-dependent cytidine deaminase inhibitor of claim 1 , wherein the nucleoside is susceptible to nucleophilic attack by a metal-bound hydroxide.

7. The context-dependent cytidine deaminase inhibitor of claim 6 , wherein the metal-bound hydroxide is zinc hydroxide.

8. The context-dependent cytidine deaminase inhibitor of claim 1 , wherein the nucleoside comprises a pyrimidine.

9. The context-dependent cytidine deaminase inhibitor of claim 1 , wherein when the nucleoside comprises a pyrimidine, and wherein nucleophilic attack occurs at C4 of the pyrimidine.

10. The context-dependent cytidine deaminase inhibitor of claim 9 , wherein the pyrimidine has an electron-withdrawing group at C4.

11. The context-dependent cytidine deaminase inhibitor of claim 1 , wherein the nucleoside comprises a base, wherein the base of the nucleoside has at least one Sp3 carbon center.

12. The context-dependent cytidine deaminase inhibitor of claim 11 , wherein the sp3 carbon center has at least one —OR group, wherein R is hydrogen, alkyl, aryl, aralkyl, alkenyl, alkynyl, or acyl.

13. The context-dependent cytidine deaminase inhibitor of claim 1 , wherein when the nucleoside comprises a pyrimidine, the nucleoside comprises a sp3 carbon center at C4 of the pyrimidine.

14. The context-dependent cytidine deaminase inhibitor of claim 1 , wherein the nucleoside comprises a base, wherein the base of the nucleoside comprises at least one group capable of hydrogen bonding.

15. The context-dependent cytidine deaminase inhibitor of claim 1 , wherein the nucleoside is selected from the group consisting of 4-fluorozebularine, 2′-deoxy, 2′-fluorozebularine, 3,4,5,6-tetrahydro-2′-deoxyuridine, nebularine; 8-azanebularine; coformycin; or zebularine.

16. The context-dependent cytidine deaminase inhibitor of claim 1 , wherein the polymeric substrate comprises oligonucleotide residues.

17. The context-dependent cytidine deaminase inhibitor of claim 1 , wherein the targeted cytidine deaminase is APOBEC-1.

18. The context-dependent cytidine deaminase inhibitor of claim 1 , wherein the targeted cytidine deaminase is AID.

19. The context-dependent cytidine deaminase inhibitor of claim 18 , comprising WRZY, wherein W is Adenine or Thymine, wherein R is a purine, wherein Z is the nucleoside, and wherein Y is a pyrimidine.

20. The context-dependent cytidine deaminase inhibitor of claim 1 , wherein the targeted cytidine deaminase is CEM15.

21. A composition comprising the context-dependent cytidine deaminase inhibitor of claim 1 and a pharmaceutical carrier.

22. A cell comprising the context-dependent cytidine deaminase inhibitor of claim 1 .

23. The context-dependent cytidine deaminase inhibitor of claim 1 , wherein the targeted cytidine deaminase is APOBEC-3F.

24. The context-dependent cytidine deaminase inhibitor of claim 1 , wherein the targeted cytidine deaminase is APOBEC-3B.