Peptide compounds and peptide conjugates for the treatment of cancer through receptor-mediated chemotherapy
The present disclosure relates to peptide compounds and conjugate compounds, processes, methods and uses thereof for treating cancer. For example, the compounds can comprise compounds of formula X 1 X 2 X 3 X 4 X 5 GVX 6 AKAGVX 7 NX 8 FKSESY (SEQ ID NO: 1) (I) (X 9 ) n GVX 10 AKAGVX 11 NX 12 FKSESY (SEQ ID NO: 2) (II) YKX 13 LRRX 14 APRWDX 15 PLRDPALRX 16 X 17 L (SEQ ID NO: 3) (III) YKX 18 LRR(X 19 ) n PLRDPALRX 20 X 21 L (SEQ ID NO: 4) (IV) IKLSGGVQAKAGVINMDKSESM (SEQ ID NO: 5) (V) IKLSGGVQAKAGVINMFKSESY (SEQ ID NO: 6) (VI) IKLSGGVQAKAGVINMFKSESYK (SEQ ID NO: 7) (VII) GVQAKAGVINMFKSESY (SEQ ID NO: 8) (VIII) GVRAKAGVRNMFKSESY (SEQ ID NO: 9) (IX) GVRAKAGVRN(Nle)FKSESY (SEQ ID NO: 10) (X) YKSLRRKAPRWDAPLRDPALRQLL (SEQ ID NO: 11) (XI) YKSLRRKAPRWDAYLRDPALRQLL (SEQ ID NO: 12) (XII) YKSLRRKAPRWDAYLRDPALRPLL (SEQ ID NO: 13) (XIII) wherein X 1 to X 21 and n can have various different values and wherein at least one protecting group and/or at least one labelling agent is optionally connected to said peptide compound at an N- and/or C-terminal end.
1. A peptide compound having: at least 92% sequence identity to a compound of formula (VI), at least 80% sequence identity to a compound of formula (X), or at least 85% sequence identity to a compound of formula (XI):
(SEQ ID NO: 6)
IKLSGGVQAKAGVINMFKSESY
(VI)
(SEQ ID NO: 10)
GVRAKAGVRN(Nle)FKSESY
(X)
(SEQ ID NO: 11)
YKSLRRKAPRWDAPLRDPALRQLL
(XI)
wherein at least one protecting group and/or at least one agent is optionally connected to said peptide compound at an N-terminal position of said peptide compound, at a C-terminal position of said peptide compound, at a free amine of said peptide compound, at a free —SH of said peptide compound, or at a free carboxyl of said peptide compound.
2. The peptide compound of claim 1 , wherein the peptide compound is represented by formula (VI) and consists of the amino acid sequence of SEQ ID NO: 6.
3. The peptide compound of claim 1 , wherein the peptide compound is represented by formula (VII) and consists of the amino acid sequence of SEQ ID NO: 7.
4. The peptide compound of claim 1 , wherein the peptide compound is represented by formula (VIII) and consists of the amino acid sequence of SEQ ID NO: 8.
5. The peptide compound of claim 1 , wherein the peptide compound is represented by formula (IX) and consists of the amino acid sequence of SEQ ID NO: 9.
6. The peptide compound of claim 1 , wherein the peptide compound is represented by formula (X) and consists of the amino acid sequence of SEQ ID NO: 10.
7. The peptide compound of claim 1 , wherein the peptide compound is represented by formula (XI) and consists of the amino acid sequence of SEQ ID NO: 11.
8. The peptide compound of claim 1 , wherein the peptide compound is represented by formula (XII) and consists of the amino acid sequence of SEQ ID NO: 12.
9. The peptide compound of claim 1 , wherein the peptide compound is represented by formula (XIII) and consists of the amino acid sequence of SEQ ID NO: 13.
10. The peptide compound of claim 1 , wherein the peptide compound has at least 90% sequence identity to the compound of formula (X) or formula (XI).
11. The peptide compound of claim 1 , wherein the peptide compound is connected to the at least one agent.
12. The peptide compound of claim 11 , wherein the peptide compound is connected to the at least one agent by a linker.
13. The peptide compound of claim 1 , wherein the peptide compound is connected to at least one protecting group.
14. The peptide compound of claim 13 , wherein the at least one protecting group is acetyl or succinyl.
15. The peptide compound of claim 14 , wherein the peptide compound is connected to the at least one protecting group to form a peptide compound-protecting group conjugate represented by Formula (XXXVIII), Formula (XXXIX), Formula (XXXX), Formula (XXXXI), Formula (XXXXII) or Formula (XXXVI):
(SEQ ID NO: 14)
Acetyl-GVRAKAGVRNMFKSESY
(XXXVIII)
(SEQ ID NO: 15)
Acetyl-GVRAKAGVRN(Nle)FKSESY
(XXXIX)
(SEQ ID NO: 16)
Acetyl-YKSLRRKAPRWDAPLRDPALRQLL
(XXXX)
(SEQ ID NO: 17)
Acetyl-YKSLRRKAPRWDAYLRDPALRQLL
(XXXXI)
(SEQ ID NO: 18)
Acetyl-YKSLRRKAPRWDAYLRDPALRPLL
(XXXXII)
Succinyl-IKLSGGVQAKAGVINMFKSESY
(XXXVI),
that comprises the peptide compound having SEQ ID NO: 6 connected to a succinyl group at the N-terminal end.
16. The peptide compound of claim 11 , wherein the peptide compound is connected to at least one therapeutic agent, labelling agent and/or imaging agent.
17. The peptide compound of claim 16 , wherein the at least one therapeutic agent is an anticancer agent.
18. A method of selectively targeting at least one agent to a sortilin-expressing cell in a population of cells, comprising contacting the peptide compound of claim 11 with the population of cells.
19. The method of claim 18 , wherein the at least one agent is at least one anticancer agent and the sortilin-expressing cell is a cancer cell.
20. A method of increasing cellular internalization of at least one agent in a sortilin-expressing cell, comprising contacting the peptide compound of claim 11 with the sortilin-expressing cell.
21. The method of claim 20 , wherein the at least one agent is at least one anticancer agent and the sortilin-expressing cell is a cancer cell.