Flexibly labeling peptides
A solid phase peptide synthesis method for synthesizing a peptidyl contrast agent is disclosed. In one example, the method includes synthesizing an amino-chelator loaded resin, coupling of the amino-chelator loaded resin to the C-terminus and/or backbone of a peptide, cleaving the amino-chelator-peptide from a resin, and chelating a lanthanide metal to the amino-chelator-peptide.
1. A SPPS method for synthesizing a peptidyl contrast agent, comprising:
synthesizing an amino-chelator loaded resin;
coupling of the amino-chelator loaded resin to the C-terminus of a peptide;
cleaving the amino-chelator-peptide from a resin; and
chelating a lanthanide metal to the amino-chelator-peptide.
2. The method of claim 1 , where the synthesizing of the amino-chelator loaded resin includes one or more of, coupling a resin to a chelator having an amine protecting group, cleaving the amine protecting group to expose an amine, reacting protected α-brominated glycine and chelator, and cleaving the protecting group.
3. The method of claim 1 , the amino-chelator loaded resin being a DOTA loaded resin.
4. The method of claim 1 , the amino-chelator loaded resin being a DTPA loaded resin.
5. The method of claim 2 , where the amine protecting group is Fmoc.
6. The method of claim 1 , where the resin is a Wang resin.
7. The method of claim 1 , the peptide being specific to a cell surface receptor.
8. The method of claim 7 , the peptide comprising of an amino acid sequence selected from the group consisting of SEQ ID Nos: 3 and 4.
9. The method of claim 1 , the peptide being capable of penetrating a cell membrane.
10. The method of claim 9 , the peptide comprising of an amino acid sequence selected from the group consisting of SEQ ID Nos: 5, 6, 7 and 8.
11. The method of claim 1 , the peptide being capable of non-specifically interacting with the extracellular matrix.
12. The method of claim 1 , the peptide being covalently modifiable by an enzyme.
13. The method of claim 12 , the peptide comprising of an amino acid sequence selected from the group consisting of SEQ ID Nos: 1, 7, 8, 9, 11, 13, 14, 15, and 16.
14. A SPPS method for synthesizing a peptidyl contrast agent, comprising:
synthesizing an amino-chelator loaded resin;
coupling the amino-chelator loaded resin within the backbone of a peptide;
cleaving the amino-chelator-peptide from a resin; and
chelating a lanthanide metal to the amino-chelator-peptide.
15. The method of claim 14 , where synthesizing of the amino-chelator loaded resin includes one or more of, adding an amine protecting group, coupling DOTA to a resin, adding CBZ-Gly(Br)-Ome, and cleaving CBZ.
16. The method of claim 14 , the amino-chelator loaded resin being a DOTA loaded resin.
17. The method of claim 14 , the amino-chelator loaded resin being a DTPA loaded resin.
18. The method of claim 15 , where the amine protecting group is Fmoc.
19. The method of claim 14 , where the resin is a Wang resin.
20. The method of claim 14 , the peptide being specific to a cell surface receptor.
21. The method of claim 20 , the peptide comprising of an amino acid sequence selected from the group consisting of SEQ ID Nos: 3 and 4.
22. The method of claim 14 , the peptide being capable of penetrating a cell membrane.
23. The method of claim 22 , the peptide comprising of an amino acid sequence selected from the group consisting of SEQ ID Nos: 5, 6, 7, and 8.
24. The method of claim 14 , the peptide being capable of non-specifically interacting with the extracellular matrix.
25. The method of claim 14 , the peptide being covalently modifiable by an enzyme.
26. The method of claim 25 , the peptide comprising of an amino acid sequence selected from the group consisting of SEQ ID Nos: 1, 7, 8, 9, 11, 13, 14, 15, and 16.