Use of peptides as transporters intended for the internalization of molecules of interest into target cells
The method pertains to a peptide including the amino acid sequence SEQ ID NO: 1, or a peptide including an amino acid sequence having 93%, in particular 95%, particularly 98% sequence identity homology with the sequence SEQ ID NO: 1, in order to obtain a transporter intended for the internalization of a molecule of diagnostic or therapeutic interest into the target cells.
1. A composition, comprising:
a target polypeptide selected from the group consisting of a mouse eukaryotic initiation factor 3 (eIF3-f) comprising SEQ ID NO: 19, human eIF3-f comprising SEQ ID NO: 20, and a protein having a 4.1 ezrin, radixin, moesin (FERM) domain comprising SEQ ID NO: 27; and
a transporter polypeptide comprising the DNA-binding domain (DB) and the leucine zipper type dimerization domain (DIM) of an EBV ZEBRA protein comprising the amino acid sequence of SEQ ID NO: 1,
wherein the target polypeptide is linked to the transporter polypeptide by a covalent bond, a non-covalent bond, an ionic bond, a hydrogen bond, or a hydrophobic bond.
2. The composition according to claim 1 , wherein the transporter polypeptide is present in the composition at a concentration of less than 1 nM.
3. The composition according to claim 1 , wherein the transporter polypeptide is present in the composition at a concentration of less than 0.1 nM.
4. The composition according to claim 1 , wherein the transporter polypeptide is present in the composition at a concentration of less than 0.03 nM.
5. The composition according to claim 1 , wherein the transporter polypeptide is present in the composition at a concentration of less than 5 nM.
6. A pharmaceutical composition, comprising the composition of claim 1 and a pharmaceutically acceptable carrier.
7. The pharmaceutical composition according to claim 6 , wherein said target polypeptide and said transporter polypeptide are in the form of a fusion protein.
8. The pharmaceutical composition according to claim 6 , said composition being formulated for a daily administration of 1 mg/m 2 to 1000 mg/m 2 .
9. A fusion protein, comprising
a target polypeptide selected from the group consisting of mammalian eukaryotic initiation factor of 3 (eIF3-f) comprising SEQ ID NO: 19, human eIF3-f comprising SEQ ID NO: 20, and a protein having a 4.1 ezrin, radixin, moesin (FERM) domain comprising SEQ ID NO: 27;
fused with a transporter polypeptide comprising the DNA-binding domain (DB) and the leucine zipper type dimerization domain (DIM) of an EBV ZEBRA protein comprising the amino acid SEQ ID NO: 1.
10. The fusion peptide according to claim 9 , wherein the target polypeptide is fused to the N-terminal end of the transporter polypeptide.
11. The fusion peptide according to claim 9 , wherein the target polypeptide is fused to the C-terminal end of the transporter polypeptide.
12. The fusion peptide according to claim 9 , comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 35, SEQ ID NO: 48, SEQ ID NO: 40, and SEQ ID NO: 53.