Compounds and methods for the detection of trpv-6 cancers and drug delivery

Abstract

Compounds containing TRPV6-binding peptides and their use in the detection and diagnosis of cancer are described. Also described are methods for detecting and staging cancer that use the compounds of the invention. Compounds containing TRPV6-binding peptides are useful for the delivery of diagnostic and therapeutic agents to cells or tumors that express TRPV6.

1 . A compound comprising a Transient Receptor Potential Vanilloid 6 (TRPV6)-binding peptide conjugated to a biomolecule, wherein the TRPV6-binding peptide comprises all or part of a peptide comprising EGKLSSNDTEGGLCKEFLHPSKVDLPR (SEQ ID NO:1). 
     
     
         2 . The compound of  claim 1 , wherein the TRPV6-binding peptide comprises from 9 to 27 amino acids of SEQ ID NO: 1. 
     
     
         3 . The compound of  claim 1 , wherein the TRPV6-binding peptide comprises a contiguous part of the C-terminal sequence of SEQ ID NO:1. 
     
     
         4 . The compound of  claim 3 , wherein the TRPV6-binding peptide comprises at least 9 contiguous amino acids of the C-terminal sequence of SEQ ID NO:1 
     
     
         5 . The compound of  claim 1 , wherein the TRPV6-binding peptide has at least 70% identity to the amino acid sequence HPSKVDLPR. 
     
     
         6 . The compound of  claim 1 , wherein the TRPV6-binding peptide comprises the amino acid sequence HPSKVDLPR. 
     
     
         7 . The compound of  claim 1 , wherein the TRPV6-binding peptide has at least 70% identity to the amino acid sequence KEFLHPSKVDLPR. 
     
     
         8 . The compound of  claim 1 , wherein the peptide comprises the amino acid sequence KEFLHPSKVDLPR. 
     
     
         9 . The compound of  claim 1 , wherein the TRPV6-binding peptide has at least 70% identity to the amino acid sequence EGKLSSNDTEGGLCKEFLHPSKVDLPR. 
     
     
         10 . The compound of  claim 1 , wherein the peptide comprises the amino acid sequence EGKLSSNDTEGGLCKEFLHPSKVDLPR. 
     
     
         11 . The compound of  claim 1 , wherein the biomolecule comprises a detectable label. 
     
     
         12 . The compound of  claim 1 , wherein the biomolecule comprises a therapeutic agent. 
     
     
         13 . The compound of  claim 12 , wherein the therapeutic agent is an anti-cancer agent. 
     
     
         14 . A pharmaceutical composition comprising the compound of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         15 . A method for detecting TRPV6 protein in a sample comprising:
 a) contacting the sample with the compound of  claim 1 ;   b) detecting the biomolecule conjugated to the TRPV6-binding peptide thereby detecting the TRPV6 protein.   
     
     
         16 . The method of  claim 15 , wherein the biomolecule comprises a fluorophore and the step of detecting the biomolecule comprises detecting the fluorophore. 
     
     
         17 . The method of  claim 15 , wherein the sample is a bodily fluid. 
     
     
         18 . The method of  claim 17 , wherein the bodily fluid is blood. 
     
     
         19 . The method of  claim 15 , wherein the biomolecule is detected in vivo. 
     
     
         20 . A method of identifying cancer in a sample from a subject comprising:
 a) detecting TRPV6 mRNA or protein in the sample;   b) comparing the amount of TRPV6 mRNA or protein in the sample with an amount of TRPV6 mRNA or protein in a control sample, wherein an increased amount of TRPV6 mRNA or protein in the sample compared to the control is indicative of cancer.   
     
     
         21 . The method of  claim 20 , wherein the step of detecting TRPV6 protein comprises contacting the sample with the compound of  claim 1 . 
     
     
         22 . The method of  claim 20 , wherein the sample is a bodily fluid. 
     
     
         23 . The method of  claim 22 , wherein the bodily fluid is blood. 
     
     
         24 . The method of  claim 20 , wherein the cancer is stage I cancer or stage II cancer. 
     
     
         25 . The method of  claim 20 , wherein the cancer is ovarian cancer, breast cancer or prostate cancer. 
     
     
         26 . A method of identifying a cancer tumor in a subject comprising:
 a) administering to the subject a compound comprising a TRPV6-binding peptide or an antibody to TRPV6;   b) detecting the TRPV6-binding peptide or antibody to TRPV6 in the subject thereby detecting TRPV6;   c) identifying regions of the subject with increased levels of TRPV6 relative to a control level, wherein increased levels of TRPV6 are indicative of a cancer tumor.   
     
     
         27 . The method of  claim 26 , wherein the compound comprises the compound of  claim 1 . 
     
     
         28 . The method of  claims 26 , wherein the cancer tumor is an ovarian cancer tumor, breast cancer tumor or a prostate cancer tumor. 
     
     
         29 . The method of  claim 26 , wherein the compound comprising a TRPV6-binding peptide or antibody to TRPV6 comprises a magnetic resonance imaging contrast agent and the step of detecting the TRPV6-binding peptide or antibody to TRPV6 comprises magnetic resonance imaging (MRI). 
     
     
         30 . The method of  claim 29 , wherein the magnetic resonance imaging contrast agent is super paramagnetic iron oxide (SPIO) 
     
     
         31 . The method of  claim 26 , wherein the compound comprising a TRPV6-binding peptide or antibody to TRPV6 comprises a fluorophore and the step of detecting the TRPV6-binding peptide or antibody to TRPV6 comprises detecting the fluorophore. 
     
     
         32 . A method of delivering a biomolecule to a cell expressing TRPV6 comprising contacting the cell with the compound of  claim 1 . 
     
     
         33 . The method of  claim 32 , wherein the biomolecule comprises a therapeutic agent. 
     
     
         34 . The method of  claim 33 , wherein the therapeutic agent comprises an anti-cancer agent. 
     
     
         35 . The method of  claim 32 , wherein the biomolecule comprises a detectable label. 
     
     
         36 . The method of  claim 35 , wherein the detectable label is a fluorophore or a magnetic resonance imaging contrast agent. 
     
     
         37 . The method of  claim 32 , wherein the step of contacting the cell occurs in vivo.