Short TAT oligomers for drug delivery
Trans-activating transcription (TAT) factor peptide oligomers coupled with functional agents can selectively complex to the anionic surface of cancerous cells. The TAT conjugates can be delivered to the locus of the tumors using intra-arterial injection during transient blood flow arrest.
1. A peptide conjugate or pharmaceutically acceptable salt thereof comprising a peptide coupled to melphalan, said peptide comprising one or more trans-activating transcription factor (TAT) sequences, wherein each TAT sequence comprises the amino acid sequence of SEQ ID NO: 8 (GRKKRRQRRRPQ).
2. The peptide conjugate or pharmaceutically acceptable salt thereof of claim 1 , further comprising a linker sequence between said melphalan and said peptide comprising one or more TAT sequences.
3. The peptide conjugate of claim 2 , wherein the linker sequence is selected from an amino acid, a peptide, and a covalent linkage.
4. The peptide conjugate or pharmaceutically acceptable salt thereof of claim 2 , wherein the linker sequence comprises one or more amino acids.
5. The peptide conjugate or pharmaceutically acceptable salt thereof of claim 2 , wherein the linker sequence comprises lysine and is located at a C-terminal end of the peptide comprising one or more TAT sequences.
6. The peptide conjugate or pharmaceutically acceptable salt thereof of claim 1 , wherein said melphalan is coupled to an N-terminal end of said peptide comprising one or more TAT sequences.
7. The peptide conjugate or pharmaceutically acceptable salt thereof of claim 1 , wherein said at least one or more TAT sequences each further comprise at least one amino acid selected from the group consisting of G, C, P, Q, and combinations thereof.
8. The peptide conjugate or pharmaceutically acceptable salt thereof of claim 1 , wherein said peptide comprises two or more TAT sequences.
9. The peptide conjugate or pharmaceutically acceptable salt thereof of claim 1 , wherein said peptide comprises two to five TAT sequences.
10. The peptide conjugate or pharmaceutically acceptable salt thereof of claim 1 , wherein said peptide comprises three TAT sequences.
11. The peptide conjugate or pharmaceutically acceptable salt thereof of claim 1 , wherein said peptide comprises four TAT sequences.
12. The peptide conjugate or pharmaceutically acceptable salt thereof of claim 1 , wherein said peptide comprises five TAT sequences.