Molecular probes and methods of use

Patent metadata

Field	Value
Publication number	US-11738099-B2
Application number	US-202117182997-A
Country	US
Kind code	B2
Filing date	Feb 23, 2021
Priority date	Aug 4, 2014
Publication date	Aug 29, 2023
Grant date	Aug 29, 2023

Abstract

A molecular probe comprising a linear peptide that includes an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 9; a contrast agent; and a non-peptide linker that covalently links the peptide to the contrast agent.

First claim

Having described the invention, the following is claimed:

1. A molecular probe comprising:
a linear peptide that includes an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 9;
a contrast agent selected from at least one of a metal chelating agent or metallofullerene; and
a non-peptide linker that covalently links the peptide to the contrast agent, the linker including a carboxamide or a maleimide.

2. The probe of claim 1 , wherein the non-peptide linker is a non-peptide aliphatic or heteroaliphatic linker.

3. The probe of claim 1 , wherein the non-peptide linker includes an alkylene dicarboxamide.

4. The probe of claim 1 , wherein the contrast agent is a magnetic resonance imaging (MRI), positron emission tomography (PET), or single photon emission computed tomography (SPECT) contrast agent.

5. The probe of claim 3 , wherein the contrast agent is a metal chelating agent selected from diethylenetriaminepentaacetate (DTPA), 1,4,7,10-tetraazadodecanetetraacetate (DOTA), 1,4,7,10-tetraazadodecane-1,4,7-triacetate (DO3A), ethylenediaminetetraacetate (EDTA), 1,4,7,10-tetraazacyclotridecanetetraacetic acid (TRITA), 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid (TETA), 1,4,7,10-tetraazadodecanetetramethylacetate (DOTMA), 1,4,7,10-tetraazadodecane-1,4,7-tri methylacetate (DO3MA), N,N′,N″,N′″-tetraphosphonatomethyl-1,4,7,10-tetraazacyclododecane (DOTP), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylene methylphosphonic acid) (DOTMP), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylene phenylphosphonic acid) (DOTPP), or N,N′-ethylenedi-L-cysteine.

6. The probe of claim 1 , having the formula:

wherein:
P 1 is a linear peptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 9;
L 1 is an optional spacer,
L 2 is an amino group of the peptide P 1 or the optional spacer if present, and
M is a metal selected from the group consisting of Gd +3 , Eu +3 , Tm +3 , Dy +3 , Yb +3 , Mn +2 , Fe +3 , 55 Co, 64 Cu, 67 Cu, 47 Sc, 66 Ga, 68 Ga, 90 Y, 97 Ru, 99 mTc, 111 In, 109 Pd, 153 Sm, 177 Lu, 186 Re, and 188 Re; or salts thereof.

7. The probe of claim 6 , wherein L 1 is selected from at least one of a polyalkyleneoxide, polyvinyl alcohol, polyethylene glycol (PEG), polypropylene glycol (PPG), co-polyethylene-polypropylene glycol, polyoxyethylene (POE), polyurethane, polyphosphazene, polysaccharides, dextran, polyvinylpyrrolidones, polyvinyl ethyl ether, polyacryl amide, polyacrylate, or polycyanoacrylates.

8. The probe of claim 1 , having the formula:

wherein:
P 1 is a linear peptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 9;
L 2 is an amino group of the peptide P 1 , and
M is a metal selected from the group consisting of Gd +3 , Eu +3 , Tm +3 , Dy +3 , Yb +3 , Mn +2 , Fe + , 55 Co, 64 Cu, 67 Cu, 47 Sc, 66 Ga, 68 Ga, 90 Y, 97 Ru, 99 mTc, 111 In, 109 Pd, 153 Sm, 177 Lu, 186 Re, and 188 Re, and
n is an integer from 0 to 100; or salts thereof.

9. The probe of claim 1 , wherein the metallofullerene is Gd3N@C80.

Assignees

• Univ Case Western Reserve

Inventors

• Lu Zheng-Rong
• Han Zheng

Classifications

• A61K49/14 Primary

  Peptides, e.g. proteins · CPC title

• A61K49/0032

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

• A61K49/0056

  Peptides, proteins, polyamino acids · CPC title

• A61K51/088

  conjugates with carriers being peptides, polyamino acids or proteins (antibodies A61K51/10) · CPC title