Decoy peptides inhibiting protein phosphatase 1-mediated dephosphorylation of phospholamban
AssigneeGwangju Institute of Science and Technology
InventorsWoo Jin Park, Roger J. Hajjar, Jae Gyun Oh
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Abstract
The present invention relates to decoy peptide or polypeptide consisting of a peptide sequence represented by the following Formula I: X1-Ala-X2—X3-Ile-Glu-X4 (I). It is noteworthy that the decoy peptide or polypeptide of the present invention significantly elevates phosphorylation levels of PLB by inhibiting PP1-mediated dephosphorylation. In addition, the decoy peptide or polypeptide provides cardio-protective effects by restoring of SERCA2a activity and inotropic effect of enhancing myocardial contractility. The present invention will contribute greatly to the prevention or treatment of diseases associated with PLB.
Claims5
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a decoy peptide or polypeptide consisting of a peptide sequence represented by the following Formula I:
- X1-Ala-X2—X3-Ile-Glu-X4 (I)
- wherein X1 represents 0-1 amino acid residue(s), X2 represents Ser, Glu, or Asp, X3 represents Thr, Glu, or Asp and X4 represents 0-3 amino acid residue(s), with the proviso that X2 is not Ser when X3 is Thr;
- wherein the decoy peptide or polypeptide inhibits protein phosphatase 1 (PP1)-mediated dephosphorylation of phospholamban (PLB) by a competitive inhibition,
- wherein neither X1 nor X4 comprise membrane-spanning domains and X1, if present, is not Tyr,
- and wherein the decoy peptide or polypeptide is linked to a cell membrane-permeable peptide.
Dependencies are inferred from the claim text.