Platelet glycoprotein

A number of promising approaches have emerged in the eady to mid-1980s that may ultimately provide an agent. In general these approaches have focused on compounds that bind to the platelet glycoprotein (GP) Ilb/Ilia receptor. This receptor on the platelet surface is responsible for its binding to... 

Deshmukh VR, Fiorella DJ, Albuquerque FC, Frey J, Flaster M, Wallace RC, Spetzler RF, McDougall CG. Intra-arterial thrombolysis for acute ischemic stroke preliminary experience with platelet glycoprotein Ilb/IIIa inhibitors as adjunctive therapy. Neurosurgery 2005 56 46-54 [discussion 54 5]. 

Junghans U, Seitz RJ, Wittsack HJ, Aulich A, Siebler M. Treatment of acute basilar artery thrombosis with a combination of systemic alteplase and tirofiban, a nonpeptide platelet glycoprotein Ilb/HIa inhibitor report of four cases. Radiology 2001 221 795-801. 

Junghans U, Siebler M. Cerebral microembohsm is blocked by tirofiban, a selective nonpeptide platelet glycoprotein Ilb/nia receptor antagonist. Circulation 2003 107 2717-2721. 

CD35 C3b receptor CD36 Known to be z macrophage thrombospondin receptor CD40 Present on B cells and follicular dendritic cells CD41 Known to be z platelet glycoprotein... 

Lefkovits J., Plow E. F., Topol E. Platelet glycoprotein Ilb/IIIa receptors in cardiovascular medicine. N Engl J Med 1995 332, 1553-9. 

Simsek S., Admiraal L. G., Modderman P. W Van der School C. E., Von dem Borne A. E. G. K. Identification of a homozygous single base pair deletion in the gene coding for the human platelet glycoprotein Iba causing Bemard-Soulier syndrome. Thromb Haemost 1994 72,444-9. 

Wright S. D., Michaelides K., Johnson D. J. D., West N. C., Tuddenham E. G. D. Double heterozygosity for mutations in the platelet glycoprotein IX gene in threee siblings with Bemard-Soulier syndrome. Blood 1993 81,2339-47. 

Miller J. L., Lyle V. A., Cunningham D. Mutation of leucine-57 to phenylalanine in a platelet glycoprotein Iba leucine tandem repeat occurring in patients with an autosomal dominant variant of Bemard-Soulier disease. Blood 1992 79,439-46. 

Jung, S.M., and Moroi, M. (1983) Cross-linking of platelet glycoprotein lb by N-succinimidyl-(4-azidop henyldithio)propionate and 3,3 -dithiobis(sulfosuccinimidyl propionate). Biochim. Biophys. Acta 761, 152-162. 

Four diastereoisomers of isoxazolinol 432 have been prepared via [3 + 2] dipolar cycloadditions of nitrile oxides. The ring 45,55 isomer shows the configuration of an isolated metabolite of roxifiban, a platelet glycoprotein receptor antagonist (470). 

Other adhesion receptors that are structurally and functionally related include the receptors for fibronectin, vitronectin, platelet glycoproteins 13b and Ilia and the VLA (very-late antigen) series. All molecules involved in adhesion recognise the RGD motif and require the divalent cations Ca2+ and Mg2+ for binding. All are dimers of glycosylated proteins with relative molecular masses 95-190 kDa. There is also some sequence homology between the /J-chain (CD18) and one chain of the fibronectin receptor. 

Simon DI, Chen Z, Xu H, et al. Platelet glycoprotein ibalpha is a counterreceptor for the leukocyte integrin Mac-1 (CDllb/CD18). JExp Med 2000 192 193-204. 

Lefkovits J, Ivanhoe RJ, Califf RM, et al. Effects of platelet glycoprotein llb/llla receptor blockade by a chimeric monoclonal antibody on acute and six-month outcomes after percutaneous transluminal coronary angioplasty for acute myocardial infarction (EPIC). Am J Cardiol 1996 77 1045-1051. 

Kiefel, V., Santoso, S., Kaufmann, E., etal., Autoantibodies against platelet glycoprotein Ib/IX A frequent finding in autoimmune toombocytopenic purpura. Br.J. Haematol. 79,256-262 (1991). 

EPIC Investigators. 1994. Use of Monoclonal Antibody Directed against the Platelet Glycoprotein Ub/llla Receptor in High-Risk Coronary Angioplasty. New England Journal of Medicine 330 956-961. 

Mark DB, Talley JD, Topol EJ, Bowman L, Lam LC, Anderson KM et al. Economic assessment of platelet glycoprotein Ilb/IIIa inhibition for prevention of ischemic complications of high-risk coronary angioplasty. EPIC Investigators. Circulation 1996 94 629-35. 

Topol EJ, Mark DB, Lincoff AM, Cohen E, Burton J, Kleiman N et al. Outcomes at 1 year and economic imphcations of platelet glycoprotein Ilb/IIIa blockade in patients undergoing coronary stenting results from a multicentre randomised trial. EPISTENT investigators. Evaluation of platelet Ilb/IIIa inhibitor for stenting. Lancet 1999 354 2019-24. 

C. Aspirin inhibits platelet cyclooxygenase. Abciximab, a monoclonal antibody, binds to and inhibits the platelet glycoprotein Ilb/IIIa receptor. Dipyridamole inhibits platelet cyclic AMP phosphodiesterase and raises cyclic AMP levels. Eptifibatide binds to the glycoprotein Ilb/IIIa complex. 

Mousa SA. Antiplatelet therapies Recent advances in the development of platelet glycoprotein Ilb/IIIa antagonists. Curr Interv Cardiol Rep 1999 1 243-252. 

Griffin, H.M., and W.H. Onwehand, A human monoclonal antibody specific for the leucine-33 (PlAl, HPA-laj form of platelet glycoprotein Ilia from a V gene phage display library. Blood, 1995. 86(12) 4430-6. 

Scheme 41 p-Tum Peptidomimetics as Platelet Glycoprotein gpIIb/IIIa Antagonists 1581... 

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