Compositions Comprising D-Amino Acid Peptides and Methods of Production and Use Thereof for Inhibiting Autoantibodies

Abstract

Compositions are disclosed that include D-amino acid peptides and that are capable of specifically binding to at least one autoantibody against a G-protein coupled receptor. The autoantibody is produced in a patient having or being predisposed to a disease condition or disorder, and the autoantibody is capable of binding to a specific epitope of the G-protein coupled receptor. Methods of production and use of said compositions are also disclosed.

1 . A composition, comprising at least one retro-inverso D-amino acid (RID) peptide capable of specifically binding to at least one autoantibody against a G-protein coupled receptor, wherein the autoantibody is produced in a patient having or being predisposed to a disease condition or disorder, the autoantibody capable of binding to a specific epitope of the G-protein coupled receptor, and the RID peptide comprising D-amino acids having a sequence that is a mirror image of at least a portion of the epitope such that the D-amino acids are in a reverse order compared to the native L-amino acid sequence of the epitope. 
     
     
         2 . The composition of  claim 1 , wherein the at least one G-protein coupled receptor is selected from the group consisting of AT1R, AT2R, β1AR, β2AR, M2R, M3R, α1AR, D1R, D2R, TSHR, β3AR, an endothelin receptor, and a thrombin receptor. 
     
     
         3 . The composition of  claim 2 , wherein at least a portion of the epitope comprises at least four consecutive amino acids of at least one of SEQ ID NOS: 1, 5-18, and 26, and wherein the RID peptide comprising a sequence of D-amino acids in retro-inverso orientation to said at least four amino acids of at least one of SEQ ID NOS:1, 5-18, and 26. 
     
     
         4 . The composition of  claim 1 , wherein the RID peptide comprises at least five D-amino acids. 
     
     
         5 . The composition of  claim 1 , wherein the RID peptide comprises at least one of SEQ ID NOS:3, 4, 19, 20, 27, and 29. 
     
     
         6 . The composition of  claim 2 , wherein the epitope is in an extracellular loop of the G-protein coupled receptor. 
     
     
         7 . The composition of  claim 1  further comprising a pharmaceutically acceptable carrier. 
     
     
         8 . The composition of  claim 7 , wherein the composition is formulated for oral administration. 
     
     
         9 . A composition, comprising a mixed L-amino acid/D-amino acid (L-AA/D-aa) peptide capable of specifically binding to at least one autoantibody at least one G-protein coupled receptor, wherein the autoantibody is produced in a patient having or being predisposed to a disease condition or disorder, the autoantibody capable of binding to a specific epitope of the G-protein coupled receptor, the peptide comprising at least a portion of the epitope formed of L-amino acids and at least one D-amino acid flanking each end of the at least a portion of the epitope. 
     
     
         10 . The composition of  claim 9 , wherein the at least one G-protein coupled receptor is selected from the group consisting of AT1R, AT2R, β1AR, β2AR, M2R, M3R, α1AR, D1R, D2R, TSHR, β3AR, an endothelin receptor, and a thrombin receptor. 
     
     
         11 . The composition of  claim 10 , wherein the epitope comprises at least four consecutive amino acids of at least one of SEQ ID NOS:1, 5-18, and 26. 
     
     
         12 - 18 . (canceled) 
     
     
         19 . A method of treating postural tachycardia syndrome (POTS) in a subject in need of such treatment, comprising:
 administering to the subject a therapeutically-effective amount of at least one retro-inverse D-amino acid (RID) peptide capable of specifically binding to at least one autoantibody against an α1AR receptor, wherein the autoantibody is capable of binding to a specific epitope of the α1AR receptor, and the RID peptide comprising D-amino acids having a sequence that is a mirror image of at least a portion of the specific epitope such that the D-amino acids are in a reverse order compared to the native L-amino acid sequence of the specific epitope.