An optimized agonist peptide of protease-activated receptor 4 and its use in a validated platelet-aggregation assay

References

• Franchi F, Rollini F, Park Y, Angiolillo DJ. Novel antiplatelet agents: the current state and what is coming down the pike. Prog Cardiovasc Dis 2015;583:267–277. DOI:10.1016/j.pcad.2015.08.009
   PubMed Web of Science ®Google Scholar
• Yang J, Xu K, Seiffert D. Challenges and promises of developing thrombin receptor antagonists. Recent Pat Cardiovasc Drug Discov 2010;53:162–170. https://www.ingentaconnect.com/content/ben/prc/2010/00000005/00000003/art00002
   PubMedGoogle Scholar
• Coughlin SR. Protease-activated receptors and platelet function. Thromb Haemost 1999;822:353–356. DOI:10.1055/s-0037-1615853
   PubMed Web of Science ®Google Scholar
• Kahn ML, Nakanishi-Matsui M, Shapiro MJ, Ishihara H, Coughlin SR. Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin. J Clin Invest 1999;1036:879–887. DOI:10.1172/JCI6042
   PubMed Web of Science ®Google Scholar
• Wong PC, Seiffert D, Bird JE, Watson CA, Bostwick JS, Giancarli M, Allegretto N, Hua J, Harden D, Guay J, et al. Blockade of protease-activated receptor-4 (PAR4) provides robust antithrombotic activity with low bleeding. Sci Transl Med 2017;9371. DOI:10.1126/scitranslmed.aaf5294
   Web of Science ®Google Scholar
• French SL, Hamilton JR. Protease-activated receptor 4: from structure to function and back again. Br J Pharmacol 2016;17320:2952–2965. DOI:10.1111/bph.13455
   PubMed Web of Science ®Google Scholar
• Eikelboom JW, Hirsh J, Spencer FA, Baglin TP, Weitz JI. Antiplatelet drugs - Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012;1412:e89S–e119S. DOI:10.1378/chest.11-2293
   PubMed Web of Science ®Google Scholar
• Morrow DA, Braunwald E, Bonaca MP, Ameriso SF, Dalby AJ, Fish MP, Fox KAA, Lipka LJ, Liu X, Nicolau JC, et al. Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med 2012;36615:1404–1413. DOI:10.1056/NEJMoa1200933
   PubMed Web of Science ®Google Scholar
• Tricoci P, Huang Z, Held C, et al. Thrombin-receptor antagonist vorapaxar in acute coronary syndromes. N Engl J Med 2012;3661:20–33. DOI:10.1056/NEJMoa1109719
   PubMed Web of Science ®Google Scholar
• Paniccia R, Priora R, Liotta AA, Abbate R. Platelet function tests: a comparative review. Vasc Health Risk Manag 2015;11:133–148. DOI:10.2147/VHRM.S44469
   PubMed Web of Science ®Google Scholar
• Born GV. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 1962;1944832:927–929. DOI:10.1038/194927b0
   PubMed Web of Science ®Google Scholar
• Vu TK, Hung DT, Wheaton VI, Coughlin SR. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell 1991;646:1057–1068. DOI:10.1016/0092-8674(91)90261-V
   PubMed Web of Science ®Google Scholar
• Vandendries ER, Hamilton JR, Coughlin SR, Furie B, Furie BC. Par 4 is required for platelet thrombus propagation but not fibrin generation in a mouse model of thrombosis. Proc Natl Acad Sci U S A 2007;1041:288–292. DOI:10.1073/pnas.0610188104
   PubMed Web of Science ®Google Scholar
• Xu WF, Andersen H, Whitmore TE, Presnell SR, Yee DP, Ching A, Gilbert T, Davie EW, Foster DC, et al. Cloning and characterization of human protease-activated receptor 4. Proc Natl Acad Sci U S A 1998;9512:6642–6646. DOI:10.1073/pnas.95.12.6642
   PubMed Web of Science ®Google Scholar
• Chen J, Bernstein HS, Chen M, Wang L, Ishii M, Turck CW, Coughlin SR, et al. Tethered ligand library for discovery of peptide agonists. J Biol Chem 1995;40:23398–23401. DOI:10.1074/jbc.270.40.23398
   PubMed Web of Science ®Google Scholar
• Seiler SM, Peluso M, Tuttle JG, Pryor K, Klimas C, Matsueda GR, Bernatowicz MS, et al. Thrombin receptor activation by thrombin and receptor-derived peptides in platelet and CHRF-288 cell membranes: receptor-stimulated GTPase and evaluation of agonists and partial agonists. Mol Pharmacol 1996;491:190–197.
   PubMed Web of Science ®Google Scholar
• Natarajan S, Riexinger D, Peluso M, Seiler SM. ‘Tethered ligand’ derived pentapeptide agonists of thrombin receptor: a study of side chain requirements for human platelet activation and GTPase stimulation. Int J Pept Protein Res 1995;452:145–151. DOI:10.1111/j.1399-3011.1995.tb01033.x
   PubMedGoogle Scholar
• Scarborough RM, Naughton MA, Teng W, Hung DT, Rose J, Vu TK, Wheaton VI, Turck CW, Coughlin SR, et al. Tethered ligand agonist peptides. Structural requirements for thrombin receptor activation reveal mechanism of proteolytic unmasking of agonist function. J Biol Chem 1992;26719:13146–13149. DOI:10.1016/S0021-9258(18)42184-9
   PubMed Web of Science ®Google Scholar
• Feng DM, Veber DF, Connolly TM, Condra C, Tang MJ, Nutt RF. Development of a potent thrombin receptor ligand. J Med Chem 1995;3820:4125–4130. DOI:10.1021/jm00020a029
   PubMed Web of Science ®Google Scholar
• Hollenberg MD. Proteinase-activated receptors: tethered ligands and receptor-activating peptides. Drug Dev Res 2003;594:336–343. DOI:10.1002/ddr.10301
   Web of Science ®Google Scholar
• Kahn ML, Zheng YW, Huang W, Bigornia V, Zeng D, Moff S, Farese RV, Tam C, Coughlin SR, et al. A dual thrombin receptor system for platelet activation. Nature 1998;3946694:690–694. DOI:10.1038/29325
   PubMed Web of Science ®Google Scholar
• Faruqi TR, Weiss EJ, Shapiro MJ, Huang W, Coughlin SR. Structure-function analysis of protease-activated receptor 4 tethered ligand peptides. Determinants of specificity and utility in assays of receptor function. J Biol Chem 2000;27526:19728–19734. DOI:10.1074/jbc.M909960199
   PubMed Web of Science ®Google Scholar
• Vassallo RR Jr., Kieber-Emmons T, Cichowski K, Brass LF. Structure-function relationships in the activation of platelet thrombin receptors by receptor-derived peptides. J Biol Chem 1992;2679:6081–6085. DOI:10.1016/S0021-9258(18)42664-6
   PubMed Web of Science ®Google Scholar
• Huang RS, Sorisky A, Church WR, Simons ER, Rittenhouse SE. “Thrombin” receptor-directed ligand accounts for activation by thrombin of platelet phospholipase C and accumulation of 3-phosphorylated phosphoinositides. J Biol Chem 1991;26628:18435–18438. DOI:10.1016/S0021-9258(18)55079-1
   PubMed Web of Science ®Google Scholar
• Ismat FA, Ma X, Wang Z, Frost CE, Ni YG, Yang J. Abstract TMP91: phase I assessment of the safety, tolerability, pharmacokinetics and pharmacodynamics of the oral protease-activated receptor-4 antagonist BMS-986120. Stroke 2016;47Suppl 1: ATMP91. DOI:10.1161/str.47.suppl_1.tmp91
   Google Scholar
• Meanwell NA. Synopsis of some recent tactical application of bioisosteres in drug design. J Med Chem 2011;548:2529–2591. DOI:10.1021/jm1013693
   PubMed Web of Science ®Google Scholar
• Kawabata A, Saifeddine M, Al-ani B, Hollenberg MD. Protease-activated receptors: development of agonists selective for receptors triggered by either thrombin (PAR1) or trypsin (PAR2). Proc West Pharmacol Soc 1997;40:49–51.
   PubMedGoogle Scholar
• Ishii K, Hein L, Kobilka B, Coughlin SR. Kinetics of thrombin receptor cleavage on intact cells. Relation to signaling. J Biol Chem 1993;26813:9780–9786. DOI:10.1016/S0021-9258(18)98415-2
   PubMed Web of Science ®Google Scholar
• Covic L, Gresser AL, Kuliopulos A. Biphasic kinetics of activation and signaling for PAR1 and PAR4 thrombin receptors in platelets. Biochemistry 2000;3918:5458–5467. DOI:10.1021/bi9927078
   PubMed Web of Science ®Google Scholar
• Soslau G, Goldenberg SJ, Class R, Jameson B. Differential activation and inhibition of human platelet thrombin receptors by structurally distinct alpha-, beta- and gamma-thrombin. Platelets 2004;153:155–166. DOI:10.1080/0953710042000199848
   PubMed Web of Science ®Google Scholar
• Sobieraj-Teague M, Eikelboom JW. Point-of-care testing for assessment of adequacy of oral antiplatelet therapy in patients with cardiovascular disease. Future Cardiol 2010;63:289–299. DOI:10.2217/fca.10.20
   PubMedGoogle Scholar
• Merali S, Wang Z, Frost C, Callejo M, Hedrick M, Hui L, Meadows Shropshire S, Xu K, Bouvier M, DeSouza MM, Yang J. New oral protease-activated receptor 4 antagonist BMS-986120: tolerability, pharmacokinetics, pharmacodynamics, and gene variant effects in humans. Platelets. 2022; Jun 26:1–0.
   PubMed Web of Science ®Google Scholar