Anti-cancer phosphorothioate-coupled peptide conjugates and methods of using the same
View Patent ↗Provided herein are, inter alia, nucleic acid-peptide conjugates including a non-cell penetrating protein (e.g., an Hdm2 targeting peptide) attached at its C-terminus to a phosphorothioate nucleic acid. Attachment of the phosphorothioate nucleic acid to the non-cell penetrating protein conveys stability to and allows for efficient intracellular delivery of the non-cell penetrating peptide. The nucleic acid-peptide conjugates provided herein including embodiments thereof are useful, inter alia, for the treatment of cancer.
1. A nucleic acid-peptide conjugate comprising:
(i) a non-cell penetrating peptide;
(ii) a phosphorothioate nucleic acid; and
(iii) a chemical linker attaching said phosphorothioate nucleic acid to the C-terminus of said non-cell penetrating peptide;
wherein said phosphorothioate nucleic acid enhances intracellular delivery of said non-cell penetrating peptide and wherein said non-cell penetrating peptide comprises the sequence of SEQ ID NO:3.
2. The conjugate of claim 1 , wherein said non-cell penetrating peptide binds an intracellular target.
3. The conjugate of claim 2 , wherein said intracellular target is Hdm2.
4. The conjugate of claim 2 , wherein said intracellular target is an Hdm2 protein comprising the amino acid sequence of SEQ ID NO:2.
5. The conjugate of claim 1 , wherein said phosphorothioate nucleic acid is about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100 or more nucleic acid residues in length.
6. The conjugate of claim 1 , wherein said phosphorothioate nucleic acid is about 20 nucleic acid residues in length.
7. The conjugate of claim 1 , wherein said phosphorothioate nucleic acid is a single stranded nucleic acid.
8. The conjugate of claim 1 , wherein said chemical linker is a covalent linker.
9. The conjugate of claim 1 , wherein said conjugate comprises a detectable moiety.
10. The conjugate of claim 1 , bound to an intracellular target.
11. A pharmaceutical composition comprising the peptide conjugate of claim 1 and a pharmaceutically acceptable carrier.