Synthesis and preliminary evaluation of [3H]PSB-0413, a selective antagonist radioligand for platelet P2Y12 receptors

Ali El-Tayeb; Kerstin J Griessmeier; Christa E Müller

doi:10.1016/j.bmcl.2005.08.104

Synthesis and preliminary evaluation of [3H]PSB-0413, a selective antagonist radioligand for platelet P2Y12 receptors

Bioorg Med Chem Lett. 2005 Dec 15;15(24):5450-2. doi: 10.1016/j.bmcl.2005.08.104. Epub 2005 Oct 5.

Authors

Ali El-Tayeb¹, Kerstin J Griessmeier, Christa E Müller

Affiliation

¹ Pharmaceutical Institute, Pharmaceutical Sciences Bonn (PSB), University of Bonn, Kreuzbergweg 26, D-53115 Bonn, Germany.

PMID: 16213725
DOI: 10.1016/j.bmcl.2005.08.104

Abstract

The selective antagonist radioligand [(3)H]2-propylthioadenosine-5'-adenylic acid (1,1-dichloro-1-phosphonomethyl-1-phosphonyl) anhydride ([(3)H]PSB-0413) was prepared by catalytic hydrogenation of its propargyl precursor with a high specific radioactivity of 74Ci/mmol. In preliminary saturation binding studies, [(3)H]PSB-0413 showed high affinity for platelet P2Y(12) receptors with a K(D) value of 4.57nM. Human platelets had a high density of P2Y(12) receptors exhibiting a B(max) value of 7.66pmol/mg of protein.

MeSH terms

Adenosine Monophosphate / analogs & derivatives
Adenosine Monophosphate / chemical synthesis
Adenosine Monophosphate / pharmacology
Blood Platelets / drug effects
Blood Platelets / physiology*
Humans
Kinetics
Purinergic P2 Receptor Antagonists*
Radioligand Assay
Receptors, Purinergic P2 / blood
Receptors, Purinergic P2Y12
Thionucleosides / chemical synthesis*
Thionucleosides / pharmacology*
Tritium

Substances

P2RY12 protein, human
PSB-0413
Purinergic P2 Receptor Antagonists
Receptors, Purinergic P2
Receptors, Purinergic P2Y12
Thionucleosides
Tritium
Adenosine Monophosphate