Assays for b-type natriuretic peptide analogues resistant to prolyl-specific dipeptidyl degradation

Abstract

The present invention describes compositions and methods for treating cardiovascular disease and myocardial infarction using dipeptidyl peptidase inhibitors. Also provided are methods for increasing natriuretic peptide function by administering one or more analogues of B type natriuretic peptide that provide increased stability in the presence of prolyl-specific dipeptidyl peptidases.

1 . A method for the treatment of cardiovascular disease comprising
 a) contacting a sample from a subject with a first antibody selected to bind biologically active forms of the natriuretic peptide of interest contacting the sample with a second antibody selected to bind all biologically active and biologically inactive forms of the natriuretic peptide of interest and performing an assay in which the signal depends upon the selected antibody specifically binding to a biologically active form of the natriuretic peptide of interest, but not specifically binding to a biologically inactive form of the natriuretic peptide of interest; and   b) administering a therapeutically effective amount of a dipeptidyl peptidase inhibitor to said subject when the presence of said biologically active form of said natriuretic peptide is present, and wherein said administration preserves the presence of said biologically active form of said natriuretic peptide.   
     
     
         2 .- 17 . (canceled) 
     
     
         18 . The method of  claim 1 , wherein said biologically active natriuretic peptide of interest is BNP-32. 
     
     
         19 . The method of  claim 1 , wherein the first and/or second antibodies are each conjugated to a detectable label. 
     
     
         20 . The method of  claim 19 , wherein the label is a fluorescent or luminescent tag, a metal, a dye, a radionuclide, or an enzyme. 
     
     
         21 . The method of  claim 1 , wherein the first and/or second antibodies are immobilized onto a solid support. 
     
     
         22 . The method of  claim 21 , wherein the solid support is a magnetic particle, a chromatographic matrix particle, the surface of an assay plate, a piece of solid substrate material, or a piece of membrane. 
     
     
         23 . The method of  claim 1 , wherein said dipeptidyl peptidase inhibitor is a dipeptidyl peptidase IV (DPPIV) inhibitor. 
     
     
         24 . The method of  claim 23 , wherein said DPPIV inhibitor is Diprotin A.