Cyclic peptides as protein targeting agents

Patent metadata

Field	Value
Publication number	US-11168115-B2
Application number	US-201414310201-A
Country	US
Kind code	B2
Filing date	Jun 20, 2014
Priority date	Jun 20, 2013
Publication date	Nov 9, 2021
Grant date	Nov 9, 2021

Abstract

Peptides having activity as protein binding agents are disclosed. The peptides have the following structure (I):including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein R, R1, L1, L2, G, M, Y1 Y2 and SEQ are as defined herein. Methods associated with preparation and use of such peptides, as well as pharmaceutical compositions comprising such peptides, are also disclosed.

First claim

What is claimed is:

1. A cyclic peptide having the following structure (I):

or a salt, tautomer or stereoisomer thereof, wherein:
L 1 and L 2 are each individually optionally substituted linker moieties, each linker moiety optionally comprising a linkage to a solid support, a linkage to a reporter moiety, a linkage to a peptide ligand, a linkage to an azide or alkyne moiety or combinations thereof;
G is a triazole;
M is methionine;
R is H, -L 3 -A or C(═O)-L 3 -A, wherein L 3 is a linker moiety and A is an alkyne or an azide, or wherein L 3 is a linker moiety comprising triazole and A is a bond to a peptide ligand;
R 1 is H or C 1 -C 6 alkyl;
y 1 and y 2 are each individually 0 or 1; and
SEQ is an amino acid sequence comprising from 2 to 20 amino acids selected from the group consisting of: D-alanine, glycine, D-leucine, D-isoleucine, D-valine, D-phenylalanine, D-tryptophan, D-arginine, D-histidine, D-lysine, D-aspartate, D-glutamate, D-asparagine, D-glutamine, D-serine, D-threonine, D-tyrosine, D-proline, L-alanine, L-leucine, L-isoleucine, L-valine, L-phenylalanine, L-tryptophan, L-arginine, L-histidine, L-lysine, L-aspartate, L-glutamate, L-asparagine, L-glutamine, L-serine, L-threonine, L-tyrosine, L-proline, hydroxyproline, carboxyglutamate, O-phosphoserine, homoserine, norleucine, methionine sulfoxide, and methionine methyl sulfonium.

2. The cyclic peptide of claim 1 , wherein L 1 , L 2 , or both, comprise one or more substituents selected from alkyl, alkyne, azide and aminocarbonyl.

3. The cyclic peptide of claim 1 , wherein L 1 , L 2 , or both, comprise a linkage selected from a linkage to a solid support, a linkage to a reporter moiety and a linkage to a peptide ligand.

4. The cyclic peptide of claim 1 , wherein L 1 and L 2 are alkylene.

5. The cyclic peptide of claim 1 , wherein the cyclic peptide has the following structure (Ia):

wherein:
R 3 is H, a linkage to a solid support, a linkage to a reporter moiety, a linkage to a peptide ligand, a linkage to an azide or alkyne moiety or combinations thereof; and
x and y are each independently an integer from 1 to 8.

6. The cyclic peptide of claim 1 , wherein SEQ comprises from 2 to 9 amino acids.

7. The cyclic peptide of claim 6 , wherein SEQ comprises from 5 to 7 amino acids.

8. The cyclic peptide of claim 1 , wherein the amino acids are selected from D and L stereoisomers of Ala, Gly, Leu, Ile, Val, Phe, Trp, Arg, His, Lys, Asp, Glu, Asn, Gln, Ser, Thr, Tyr and Pro.

9. The cyclic peptide of claim 1 , wherein R is H or —C(═O)-L 3 -A, where L 3 is a linker moiety and A is a bond to a peptide ligand or an alkyne.

10. The cyclic peptide of claim 9 , wherein A is an alkyne.

11. The cyclic peptide of claim 1 , wherein SEQ has 90% sequence identity to an amino acid sequence comprising any one of SEQ ID NOS: 1-33.

12. The cyclic peptide of claim 11 , wherein SEQ comprises any one of SEQ ID NOS: 1-14.

13. The cyclic peptide of claim 1 , wherein y 1 and y 2 are each 0.

14. A composition comprising the cyclic peptide of claim 1 and a pharmaceutically acceptable carrier.

15. The cyclic peptide of claim 1 , wherein the cyclic peptide comprises a linkage to a reporter moiety, the reporter moiety selected from polyethylene glycol (PEG), biotin, thiol and fluorophores.

16. The cyclic peptide of claim 15 , wherein the fluorophores are selected from carboxyfluorescein (FAM), fluorescein isothiocyanate (FITC), Cyanine-5 (Cy5), tetramethylrhodamine (TRITC) and Carboxytetramethylrhodamine (TAMRA).

17. The cyclic peptide of claim 7 , wherein the amino acids are selected from D and L stereoisomers of Ala, Gly, Leu, Ile, Val, Phe, Trp, Arg, His, Lys, Asp, Glu, Asn, Gln, Ser, Thr, Tyr and Pro.

Assignees

• California Inst Of Techn

Inventors

• Heath James R
• Rohde Rosemary Dyane
• Nag Arundhati
• Das Samir
• Umeda Aiko

Classifications

• A61K49/0032 Primary

  Methine dyes, e.g. cyanine dyes · CPC title

• C07K14/001

  by chemical synthesis · CPC title

• A61K49/0043

  Fluorescein, used in vivo · CPC title

• C07K7/56

  the cyclisation not occurring through 2,4-diamino-butanoic acid · CPC title

• C07K1/047

  Simultaneous synthesis of different peptide species; Peptide libraries · CPC title