Random peptides that bind to gastro-intestinal tract (GIT) transport receptors and related methods

Abstract

This invention relates to proteins (e.g., peptides) that are capable of facilitating transport of an active agent through a human or animal gastro-intestinal tissue, and derivatives (e.g., fragments) and analogs thereof, and nucleotide sequences coding for said proteins and derivatives. The proteins of the invention have use in facilitating transport of active agents from the lumenal side of the GIT into the systemic blood system, and/or in targeting active agents to the GIT. Thus, for example, by binding (covalently or noncovalently) a protein of the invention to an orally administered drug, the drug can be targeted to specific receptor sites or transport pathways which are known to operate in the human gastrointestinal tract, thus facilitating its absorption into the systemic system.

1 . (canceled)  
     
     
         2 . A protein which specifically binds to a gastro-intestinal transport receptor selected from the group consisting of HPT1, hPEPT1, D2H, and hSI, in which the protein comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 1-55 or a binding portion thereof.  
     
     
         3 - 22 . (canceled)  
     
     
         23 . A composition comprising the protein of  claim 2  bound to a material comprising a drug, said drug being of value in the treatment of a mammalian disease or disorder.  
     
     
         24 - 41 . (canceled)  
     
     
         42 . An antibody which is capable of immunospecifically binding the protein of  claim 2 .  
     
     
         43 - 47 . (canceled)  
     
     
         48 . A nucleic acid comprising a nucleotide sequence selected from the group consisting of SEQ ID NOS: 55-163.  
     
     
         49 - 52 . (canceled)  
     
     
         53 . The nucleic acid of  claim 48  which is isolated.  
     
     
         54 - 56 . (canceled)  
     
     
         57 . A nucleic acid comprising a nucleotide sequence encoding a chimeric protein comprising at least 6 contiguous amino acids of an amino acid sequence selected from the group consisting of SEQ ID NOS: 1-55, that specifically bind to a gastro-intestinal tract receptor fused via a covalent bond to an amino acid sequence of a second protein.  
     
     
         58 - 60 . (canceled)  
     
     
         61 . A recombinant cell containing the nucleic acid of  claim 48  or  57 .  
     
     
         62 - 63 . (canceled)  
     
     
         64 . A method of producing a protein comprising growing a recombinant cell containing the nucleic acid of  claim 48  or  57  such that the encoded protein is expressed by the cell, and recovering the expressed protein.  
     
     
         65 - 66 . (canceled)  
     
     
         67 . The product of the process of  claim 64 .  
     
     
         68 - 75 . (canceled)  
     
     
         76 . A method of treating or preventing a disease or disorder comprising administering to a subject in which such treatment or prevention is desired a therapeutically effective amount of the composition of  claim 23 .  
     
     
         77 - 78 . (canceled)  
     
     
         79 . The method according to  claim 76  in which the disease or disorder is selected from the group consisting of: hypertension, diabetes, osteoporosis, hemophilia, anemia, cancer, migraines, and angina pectoris.  
     
     
         80 . The method according to  claim 76  in which the subject is a human.  
     
     
         81 - 83 . (canceled)  
     
     
         84 . A method of detecting or measuring the level of a gastro-intestinal tract receptor in a sample, comprising contacting a sample suspected of containing a gastro-intestinal tract receptor with the protein of  claim 2  under conditions conductive to binding between the protein and any of said receptor in said sample, and detecting or measuring any of said binding that occurs, in which the detected or measured amount of binding indicates the presence or amount of the receptor in the sample.  
     
     
         85 . A method of identifying a molecule that specifically binds to a ligand selected from the group consisting of the protein of  claim 2  a fragment of said protein comprising a domain of the protein, and a nucleic acid encoding said protein or fragment, comprising 
 (a) contacting said ligand with a plurality of molecules under conditions conducive to binding between said ligand and the molecules; and    (b) identifying a molecule within said plurality that specifically binds to said ligand.    
     
     
         86 . (canceled)  
     
     
         87 . A cell containing and capable of expressing a recombinant nucleic acid encoding a fragment of a gastro-intestinal tract receptor selected from the group consisting of HPT1, hPEPT1, D2H, and hSI, or encoding a chimeric protein comprising said fragment, said fragment consisting essentially of the extracellular domain of the receptor.  
     
     
         88 . (canceled)  
     
     
         89 . A method for identifying a molecule that specifically binds to a gastro-intestinal tract receptor comprising contacting a fragment of the receptor, or a chimeric protein comprising said fragment, with a plurality of test molecules under conditions conducive to binding between said fragment or protein and the molecules, and identifying a molecule within said plurality that specifically binds to said fragment or protein, in which the fragments consist of essentially of the extracellular domain of the receptor.  
     
     
         90 - 97 . (canceled)