Synthesis of heparin-like antithrombotics having perphosphorylated thrombin binding domains.
The synthesis of three heparin analogues (i.e. compounds VI-VIII) having perphosphorylated thrombin binding domains (TBDs) is reported. These compounds were tested in vitro for their antithrombin III (ATIII)-mediated anti-Xa and antithrombin activities. Conjugates VI and VIII show a remarkable increase in antithrombin activity compared to the structurally related conjugates with persulfated TBDs (i.e. compounds IV and V), whereas compound VII displays a diminished activity.
Buijsman
R C
RC
Leiden Institute of Chemistry, Gorlaeus Laboratories, The Netherlands.
Basten
J E
JE
Dreef-Tromp
C M
CM
van der Marel
G A
GA
van Boeckel
C A
CA
van Boom
J H
JH
D000991:Antithrombins / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D006493:Heparin / Q000031:analogs & derivatives*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010766:Phosphorylation; D013917:Thrombin / Q000378:metabolism*
D000991:Antithrombins; D006493:Heparin; D013917:Thrombin