Cyclic peptide binder against oncogenic K-Ras

Patent metadata

Field	Value
Publication number	US-10017540-B2
Application number	US-201615068528-A
Country	US
Kind code	B2
Filing date	Mar 11, 2016
Priority date	Mar 11, 2015
Publication date	Jul 10, 2018
Grant date	Jul 10, 2018

Abstract

Cyclic peptides represented by (Formula 1)

selectively bind the oncoprotein K-Ras G12D in vitro and in cellulo, where Z1 and Z2 are each L-propargylglycine (Pra), azidoornithine (OrnN3), or L-azidolysine (Az4), and V1-V2-V3-V4-V5 is an amino acid variable region having a sequence selected from the group consisting of SEQ ID NOs: 1-20.

First claim

What is claimed is:

1. A cyclic peptide represented by Formula I:

wherein: Z1 and Z2 are each L-propargylglycine (Pra), azidoornithine (OrnN3), or L-azidolysine (Az4), wherein when Z1 is Pra, Z2 is OrnN3 or Az4, when Z1 is OrnN3 or Az4, Z2 is Pra; and V1-V2-V3-V4-V5 is a five amino acid variable region having a sequence selected from the group consisting of SEQ ID NOs: 1-20; L is a linker moiety; and B m is an optional detection group, wherein m is 0 or 1.

2. The cyclic peptide of claim 1 , wherein Z1 is Pra and Z2 is Az4.

3. The cyclic peptide of claim 1 , wherein Z1 is Pra and Z2 is OrnN3.

4. The cyclic peptide of claim 1 , wherein Z1 is Az4 and Z2 is Pra.

5. The cyclic peptide of claim 1 , wherein V1-V2-V3-V4-V5 is SEQ ID NO: 7, 11, or 16.

6. The cyclic peptide of claim 1 , wherein L is 1,4-triazole.

7. The cyclic peptide of claim 6 , wherein when m is 1, the optional detection group is a detection tag, a detection tag, or a combination of a spacer group and a detection tag.

8. The cyclic peptide of claim 7 , wherein the spacer group is polyethylene glycol (PEG) or 6-aminohexanoic acid (Ahx).

9. The cyclic peptide of claim 7 , wherein the detection tag is an affinity tag, a fluorescent tag, or a fluorescently labeled affinity tag.

10. The cyclic peptide of claim 7 , wherein the detection tag is an affinity tag selected from the group consisting of biotin, streptavidin, poly-histidine, poly-arginine, FLAG, cyclodextrin, adamantane, and combinations thereof.

11. The cyclic peptide of claim 7 wherein the spacer group is PEG and the detection tag is biotin.

Assignees

• California Inst Of Techn

Inventors

• Henning Ryan K
• Ram Ashwin N
• Das Samir
• Nag Arundhati
• Heath James R

Classifications

• G01N2333/914

  Hydrolases (3) · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C07K7/64 Primary

  Cyclic peptides containing only normal peptide links · CPC title

• G01N2500/04

  Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A) · CPC title

• G01N2333/82

  Translation products from oncogenes · CPC title