Single domain tdf-related compounds and analogs thereof

Abstract

The present invention relates generally to tissue differentiation factor (TDF) analogs. More specifically, the invention relates to structure-based methods and compositions useful in designing, identifying, and producing molecules which act as functional modulators of TDF-like receptors. The invention further relates to methods of detecting, preventing, and treating TDF-associated disorders.

1 . A compound comprising an amino acid sequence selected from the group consisting of, SEQ ID NOs:1-208, polynucleotides encoding SEQ ID NOs:1-208, and variants, analogs, homologs, or fragments thereof. 
     
     
         2 . The compound of  claim 1 , wherein the compound modulates signal transduction across a membrane of a cell that expresses a tissue differentiation factor receptor. 
     
     
         3 . An isolated nucleic acid encoding the compound of  claim 1 . 
     
     
         4 . A vector comprising the nucleic acid of  claim 3 . 
     
     
         5 . The vector of  claim 4 , further comprising a promoter operably linked to the nucleic acid molecule. 
     
     
         6 . A cell comprising the vector of  claim 5 . 
     
     
         7 . A pharmaceutical composition comprising a compound of  claim 1 , and a pharmaceutically acceptable carrier. 
     
     
         8 - 12 . (canceled) 
     
     
         13 . A method for preparing a compound, the method comprising: (a) culturing a cell containing a nucleic acid according to  claim 5  under conditions that provide for expression of the compound; and (b) recovering the expressed compound. 
     
     
         14 - 15 . (canceled) 
     
     
         16 . A method of identifying a compound that binds to a compound of  claim 1 , the method comprising: (a) contacting the compound with the compound of  claim 1 ; and (b) determining whether the compound binds to the compound of  claim 1 . 
     
     
         17 . A method of treating or preventing a tissue differentiation factor-associated disorder, the method comprising administering to a subject in which such treatment or prevention is desired the compound of  claim 1  in an amount sufficient to treat or prevent the tissue differentiation factor-associated disorder in the subject. 
     
     
         18 . The method of  claim 17 , wherein the tissue differentiation factor-associated disorder is selected from the group consisting of a tissue degenerative disease and tissue regeneration. 
     
     
         19 . The method of  claim 18 , wherein the tissue degenerative disease is selected from the group consisting of renal disease, traumatic brain injury, stroke, atherosclerosis, arthritis, emphysema, osteoporosis, cardiomyopathy, cirrhosis, degenerative nerve disease, Holt-Oram disease, eye disease, diabetic nephropathy, degenerative bone disease, renal disease, periodontal disease, diabetic nephropathy, diabetes, atherosclerosis, cardiovascular disease, inflammatory disease, immune disease, skeletal disease, reproductive disease, haematopoietic disease, and cancer. 
     
     
         20 . The method of  claim 18  wherein the tissue regeneration is selected from the group consisting of muscle, dendritic tissue, nerve, kidney, brain, bone, skin, lung, muscle, ovary, testes, heart, spleen, cartilage, nerve, peridontal, dentin, liver, vascular, connective, lymphatic, haematopoietic, and renal tissue. 
     
     
         21 . The method of  claim 17 , wherein the subject is a human. 
     
     
         22 . A method of treating or preventing a tissue differentiation factor-associated disorder, the method comprising administering to a subject in which such treatment or prevention is desired the nucleic acid of  claim 5  in an amount sufficient to treat or prevent the tissue differentiation factor-associated disorder in the subject. 
     
     
         23 . The method of  claim 22 , wherein the subject is a human. 
     
     
         24 . A kit comprising in one or more containers, the pharmaceutical composition of  claim 7  and instructions for using the contents therein. 
     
     
         25 - 27 . (canceled) 
     
     
         28 . A method of treating a pathological state in a mammal, the method comprising administering to the mammal a compound in an amount that is sufficient to alleviate the pathological state, wherein the compound is a compound having an amino acid sequence at least 90% identical to a compound comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:1-208. 
     
     
         29 . (canceled) 
     
     
         30 . A method of treating a tissue differentiation factor-associated disorder in a mammal, the method comprising administering to the mammal at least one compound which modulates the expression or activity of a compound selected from the group consisting of SEQ ID NOs:1-208, or a fragment, variant, or homolog thereof. 
     
     
         31 . The method of  claim 30 , wherein the tissue differentiation factor-associated disorder is selected from the group consisting of renal disease, traumatic brain injury, stroke, atherosclerosis, arthritis, emphysema, osteoporosis, cardiomyopathy, cirrhosis, degenerative nerve disease, Holt-Oram disease, eye disease, diabetic nephropathy, degenerative bone disease, renal disease, periodontal disease, diabetic nephropathy, diabetes, atherosclerosis, cardiovascular disease, inflammatory disease, immune disease, skeletal disease, reproductive disease, haematopoietic disease, and cancer. 
     
     
         32 . A compound for use in treating a tissue differentiation factor-associated disorder, wherein the compound is selected from the group consisting of SEQ ID NOs:1-208. 
     
     
         33 . The use of a compound for the manufacture of a medicament for treatment of a tissue differentiation factor-associated disorder, wherein the compound is selected from the group consisting of SEQ ID NOs:1-208. 
     
     
         34 - 40 . (canceled)