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. Author manuscript; available in PMC: 2013 Jul 3.
Published in final edited form as: Circulation. 2012 Jun 15;126(1):83–91. doi: 10.1161/CIRCULATIONAHA.112.091918

Figure 1.

Figure 1

Structure and anti-platelet effects of the cell-penetrating PAR1 pepducin, PZ-128. A, Depiction of the mechanism of action of the cell-penetrating PZ-128 pepducin targeting the third intracellular loop (red) of PAR1. B, The NMR structure of PZ-128 was determined by simulated annealing methods using 210 distance restraints and included restraints to the proximal 3 hydrocarbons of the lipid. C, PZ-128 (green) had an RMSD of 1.4 Å with the corresponding peptide backbone region of PAR1 (red) residues 307-313 modeled on the 2.8 Å x-ray structure of rhodopsin in the off-state. D, PZ-128 inhibits PAR1-dependent platelet aggregation. Gel filtered human platelets were treated with various concentrations of PZ-128 and then challenged with the PAR1 agonist SFLLRN (2.5 μM), 20 μM ADP, 200 μM AYPGKF or 1 mg/ml Ristocetin. E, Human platelets were treated with 3 μM PZ-128, 3 μM RWJ-56110, or 5% dextrose vehicle before the addition of various concentrations of thrombin (n=3-5).