Pharmacology and In Vivo Efficacy of Pepducins in Hemostasis and Arterial Thrombosis

Acknowledgments ............................................................................................ 255

References ........................................................................................................ 255

Although remarkably diverse in sequence and function, all G protein-coupled

receptors (GPCRs) share a highly conserved topological arrangement of a seven-

transmembrane helical core domain joined by three intracellular loops, three extra-

cellular loops, and amino-and carboxyl-terminal domains.1 Overwhelming evidence

suggests that most, if not all, GPCRs have a strong propensity to dimerize and/or form

large oligomeric structures2 that can lead to cooperative binding of ligands to the

dimeric unit. A key event for the switch from inactive to active receptor is ligand-

induced conformational changes of transmembrane helices 6 (TM6), TM2, and

TM7.3 In turn, these helical movements alter the conformation of the intracellular

loops of the receptor to promote activation of associated heterotrimeric G proteins.