Compositions and methods related to profiling a plurality of cells based on peptide binding

Abstract

Methods and compositions are described for classifying cells and/or peptides that associate or bind with a particular characteristic pattern to a plurality of cells or cell lines. Aspects of the invention also include the use of peptide(s) having an appropriate binding characteristic to deliver a drug to a cell or cell population.

1 . A method of profiling cell lines comprising:
 a) providing a plurality of cell lines;   b) contacting each cell line with a library of phage displaying random heterologous peptides on their surface;   c) obtaining phage that bind each of the cell lines;   d) identifying peptides that bind each cell line; and   e) classifying each cell line based on the identified peptides.   
     
     
         2 . The method of  claim 1 , further comprising classifying each identified peptide based on the cell lines that bind each identified peptide. 
     
     
         3 . The method of  claim 1 , wherein the panel includes cancer cell lines. 
     
     
         4 . The method of  claim 3 , wherein the cancer cell lines include kidney, breast, colon, lung, prostate, brain, liver, pancreatic, uterine, neuronal, skin, head and neck, leukemic, lymphocytic, or ovarian cancer cell lines. 
     
     
         5 . The method of  claim 3 , wherein the panel is cancer cell lines. 
     
     
         6 . The method of  claim 5 , wherein the panel is a NCI 60 panel of cancer cell lines. 
     
     
         7 . The method of  claim 3 , further comprising identifying a peptide that binds to a majority of the cancer cell lines or cancer cells of common origin. 
     
     
         8 . The method of  claim 1 , further comprising analyzing the identified peptides to identify similarities with known receptor ligands. 
     
     
         9 . The method of  claim 1 , wherein classifying the cell line is performed by clustering analysis. 
     
     
         10 . The method of  claim 9 , wherein the clustering analysis is used to construct a clustered image map. 
     
     
         11 . The method of  claim 2 , wherein classifying the identified peptide is performed by clustering analysis. 
     
     
         12 . The method of  claim 11 , wherein the clustering analysis is used to construct a clustered image map. 
     
     
         13 . The method of  claim 1 , further comprising identifying receptors for at least one of the identified peptides comprising the steps of:
 a) providing an identified peptide;   b) labeling the identified peptide;   c) contacting an appropriate cell line with the labeled peptide;   d) isolating a receptor-peptide complex; and   e) identifying the receptor bound to the labeled peptide.   
     
     
         14 . A group of peptides comprising five or more peptides that selectively bind to a sub-population of cell lines, wherein the peptides comprise those listed in Table 3. 
     
     
         15 . A method of classifying a cell or cell line comprising:
 a) contacting the cell with a group of selected peptides or polypeptides that differentially bind cells of a known origin;   b) detecting the peptides or polypeptides that bind the cell line; and   c) assessing the classification of the cell or cell line based on the peptide(s) that bind the cell.   
     
     
         16 . The method of  claim 15 , wherein the selected peptides or polypeptides are phage particles. 
     
     
         17 . The method of  claim 15 , wherein the selected peptides or polypeptides are labeled. 
     
     
         18 . The method of claim  175 , wherein the selected peptides or polypeptides are labeled with a fluorophor, an enzyme or a radioisotope. 
     
     
         19 . The method of  claim 15 , wherein the group of selected peptides or polypeptides comprise at least 3 different peptides or polypeptides. 
     
     
         20 . The method of  claim 15 , wherein the selected peptides or polypeptides comprise are cyclic. 
     
     
         21 . The method of  claim 15 , wherein the selected peptides or polypeptides comprise at least 3 of the amino acid sequences from Table 3. 
     
     
         22 . The method of  claim 15 , wherein the cell or cell line is a cancer cell or cancer cell line. 
     
     
         23 . The method of  claim 15 , wherein classifying a cell comprises determineing the tissue origin of the cell or whether the cell expresses a particaulr receptor. 
     
     
         24 . The method of  claim 15 , wherein classifying a cell comprises determineing wether the cell is resistant to an anti cancer therapy. 
     
     
         25 . The method of  claim 15 , wherein the selected peptides or polypeptides differentially bind to a panel of cells of a known origin. 
     
     
         26 . A method of classifying a peptide comprising:
 a) contacting a plurality of cell lines with a library of peptides that differentially bind the cells;   b) detecting the peptides that bind the cell line; and   c) classifying the peptides based on the cells that bind the peptide.   
     
     
         27 . An EphA5 receptor targeting peptide comprising a peptide sequence of CSGIGSGGC or CRFESSGGC. 
     
     
         28 . The peptide of  claim 27 , wherein the peptide is cyclic. 
     
     
         29 . The peptide of  claim 27 , further comprising a therapeutic. 
     
     
         30 . The peptide of  claim 29 , wherein the therapeutic is a small molecule or a therapeutic polypeptide. 
     
     
         31 . The peptide of  claim 27 , further comprising an imaging agent.