Peptides and compounds that bind to elongation initiation factor 4E
View Patent ↗A peptide that binds to elongation initiation factor 4E (eIF4E) comprising the amino acid sequence CEX 1 GX 2 X 3 X 4 X 5 C (SEQ ID NO: 1), where X 1 is an amino acid selected from the group consisting of threonine (T), methionine (M) or leucine (L), X 2 and X 3 is an amino acid selected from the group consisting of phenylalanine (F), modified phenylalanine and tyrosine (Y), X 4 and X 5 is any amino acid, wherein the two cysteine residues are joined by a disulphide bond. Further, pharmaceutical compositions and uses of the peptide, and pharmaceutical compositions are provided.
1. A peptide comprising the amino acid sequence CEX1GX2X3X4X5C (SEQ ID NO: 1),
wherein X 1 is an amino acid selected from the group consisting of threonine (T), methionine (M), and leucine (L);
wherein X 2 is an amino acid selected from the group consisting of a hydrophobic amino acid, an aromatic amino acid, a modified hydrophobic amino acid, and a modified aromatic amino acid;
wherein X 3 is an amino acid selected from the group consisting of a hydrophobic amino acid, an aromatic amino acid, a modified hydrophobic amino acid, and a modified aromatic amino acid;
wherein X 4 is any amino acid;
wherein X 5 is any amino acid;
wherein the two cysteine residues are joined by a disulfide bond;
wherein the peptide binds to elongation initiation factor 4E (elF4E); and
wherein X 2 and X 3 are independently selected from the group consisting of phenylalanine (F), tyrosine (Y) and a modified phenylalanine.
2. The peptide according to claim 1 , wherein the peptide binds to elF4E at the mRNA 5′ cap-binding site.
3. The peptide according to claim 1 , wherein binding of the peptide to elF4E inhibits elF4E activity.
4. The peptide according to claim 1 , wherein the peptide binds to elF4E in an open conformation.
5. The peptide according to claim 1 , wherein X 1 is methionine (M).
6. The peptide according to claim 1 , wherein X 4 and X 5 are independently glutamine (Q), aspartic acid (D), alanine (A), lysine (K), glycine (G), or leucine (L).
7. The peptide according to claim 1 , wherein X 5 is D-aspartic acid or L-aspartic acid.
8. The peptide according to claim 1 , wherein the peptide comprises an amino acid sequence selected from the group consisting of ACEMGFFQDCG (SEQ ID NO: 2), CEMGFFQDCG (SEQ ID NO: 3), ACEMGFFADCG (SEQ ID NO: 4), ACEMGFFKDCG (SEQ ID NO: 5), ACEMGFFLDCG (SEQ ID NO: 6), CEMGFFADC (SEQ ID NO:7), ACEMGYFQDCG (SEQ ID NO: 28), and ACEMGFYQDCG (SEQ ID NO: 32).
9. The peptide according to claim 1 , wherein the peptide consists of the amino acid sequence CEMGFFADC (SEQ ID NO: 7).
10. The peptide according to claim 1 , wherein the peptide is conjugated to one or more additional peptides.
11. The peptide according to claim 10 , wherein the one or more additional peptides is a cell penetrating peptide.
12. The peptide according to claim 1 for use as a medicament.
13. A pharmaceutical composition comprising the peptide according to claim 1 and a pharmaceutically acceptable carrier.