Sulfhydryl analogues of adenosine diphosphate: chemical synthesis and activity as platelet-aggregating agents

2-Thioadenosine 5'-diphosphate (2-SH ADP), 2,2'-dithiobisadenosine 5'-diphosphate (2,2'-(S-ADP)2), 8-thioadenosine 5' diphosphate (8-SH ADP), and 6-mercaptopurine riboside 5'-disphosphate (6-MPRDP) were synthesized as potential affinity labels for ADP receptors on the blood-platelet membrane. The mean relative activities of these compounds in aggregating human platelets suspended in homologous plasma were 155% (2,2'-(S-ADP)2), 74% (2-SH ADP), 0.65% (8-SH ADP), and 0.08% (6-MPRDP). The mean relative activities against washed platelets were 249% (2,2"-(S-ADP)2) and 115% (2-SH ADP), whereas no aggregation occurred with 8-SH ADP or 6-MPRDP. The last two compounds were found to be weak inhibitors of ADP-induced aggregation. Therefore, thio-substitution at postition 2 followed by oxidation to a disulfide appears to be the most promising approach to further studies of affinity labelling of membrane ADP-receptors.