Q: What is the targeted pathway for Decoy Technology?

Answer: The decoy peptide mimics a functional receptor on a cell. They can attract certain
ligands, such as inflammatory cytokines or enzymes and compete with target receptors.
Decoy peptides are designed to trap specific ligand molecules as efficiently as their receptors.
Thus, ligand binding to the functional receptor is inhibited, and the corresponding signalling
pathway is shut down. The decoy peptide was derived from the Phospholamban (PLB)
protein sequence surrounding the Ser16 phosphorylation site. Phospholamban is cardiac
muscle protein that binds to sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) and
reduces its ability to transport calcium ions into the SR. When the heart needs to relax,
calcium ions must be actively removed from the cytoplasm and pumped back into the SR to
allow the muscle to relax and prepare for the next contraction. When the heart needs to relax,
calcium ions must be actively removed from the cytoplasm and pumped back into the SR to
allow the muscle to relax and prepare for the next contraction.
In Atherosclerosis, Decoy peptide targets Protein Phosphatase 1 (PP1).
Abnormal Vascular smooth muscle cell (VSMC) proliferation is a significant pathological
factor for atherosclerosis. when the arterial wall is damaged, VSMC migrate into the intimal
layer of the arterial wall and undergo drastic changes in their phenotype from contractile and
quiescent to synthetic and proliferative. The proliferation of VSMC is associated with a
chronic increase in the cytosolic Ca2+ level, which is caused by the loss of Ca2+ handling
proteins, such as sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a). Therefore,
maintaining a low cytosolic Ca2+ level by controlling SERCA2a activity is a reasonable
strategy to prevent VSMC proliferation.
The activity of SERCA2a in generally inhibited by a direct interaction with Phospholamban
(PLB), whose inhibitory activity is enhanced by dephosphorylation at Ser16 by protein
phosphatase 1 (PP1). Therefore, Decoy peptide target to inhibit the PP1-mediated
dephosphorylation of PLB and normalize the activity of SERCA2a in the cardiac myocyte.