Biologically cleavable tetrapeptide linking agents
View Patent ↗Tetrapeptide linkers for reversibly linking a first compound to a amine-containing second compound are described. Compounds containing the tetrapeptide linkers and methods of using the tetrapeptide linkers are also described.
1. A tetrapeptide linker comprising the structure represented by:
2. The tetrapeptide linker of claim 1 , wherein the tetrapeptide linker is linked to: (a) a first compound that comprises a targeting group, a steric stabilizer, a polynucleotide, a polymer, a polyamine, an antibody, a drug product, a hapten, a digoxigenin, a vitamin, a biotin, a fluorophore, an antibody, a monoclonal antibody, or an antibody fragment; and (b) a second compound that comprises a targeting group, a steric stabilizer, a polynucleotide, a polymer, a polyamine, an antibody, a drug product, a hapten, a digoxigenin, a vitamin, a biotin, a fluorophore, an antibody, a monoclonal antibody, or an antibody fragment.
3. The tetrapeptide linker of claim 2 , wherein the tetrapeptide linker is linked to the first compound and/or to the second compound via an amide bond.
4. The tetrapeptide linker of claim 2 , wherein the second compound comprises a polyamine.
5. The tetrapeptide linker of claim 2 , wherein the first compound and/or the second compound comprises a targeting group.
6. The tetrapeptide linker of claim 5 , wherein the targeting group comprises a cell receptor ligand.
7. The tetrapeptide linker of claim 2 , wherein the first compound and/or the second compound comprises a drug product.
8. The tetrapeptide linker of claim 2 , wherein the first compound and/or the second compound comprises a steric stabilizer.
9. The tetrapeptide linker of claim 8 , wherein the steric stabilizer is polyethylene glycol (PEG).
10. The tetrapeptide linker of claim 2 , wherein the first compound and/or the second compound comprises a cell receptor ligand having affinity for an integrin.
11. The tetrapeptide linker of claim 10 , wherein the integrin is an αvβ3 integrin.
12. The tetrapeptide linker of claim 10 , wherein the integrin is an αvβ6 integrin.
13. The tetrapeptide linker of claim 10 , wherein the cell receptor ligand having affinity for an integrin comprises an RGD-containing peptide.
14. The tetrapeptide linker of claim 2 , wherein the first compound and/or the second compound comprises an asialoglycoprotein receptor (ASGPr) ligand.
15. The tetrapeptide linker of claim 13 , wherein the asialoglycoprotein receptor (ASGPr) ligand comprises N-acetylgalactosamine.
16. The tetrapeptide linker of claim 2 , wherein the first compound and/or the second compound comprises a polynucleotide.
17. The tetrapeptide linker of claim of claim 15 , wherein the polynucleotide is an RNAi trigger.
18. The tetrapeptide linker of claim 1 , wherein the tetrapeptide linker is linked to an RNAi trigger and to a targeting group.
19. The tetrapeptide linker of claim 18 , wherein the targeting group comprises a cell receptor ligand.
20. The tetrapeptide linker of claim 19 , wherein the cell receptor ligand comprises an asialoglycoprotein receptor (ASGPr) ligand and/or a ligand having affinity for an integrin.
21. A method of inhibiting expression of a gene, the method comprising administering to a subject a composition comprising the tetrapeptide linker of claim 18 .