Cloning, purification and biochemical characterization of a thrombus-ditargeting thrombolytic agent, comprised of annexin B1, ScuPA-32K and fibrin-adherent peptide.
The development of thrombolytic agent could provide invaluable progress for antithrombotic therapy. In this paper, we reported the cloning, purification and biochemical characterization of AnxB1ScuPAFap, a thrombus-ditargeting chimera composed of annexin B1, low molecular single-chain urokinase (ScuPA-32K) and fibrin-adherent peptide (dodecapeptide, Fap). In vitro test showed that, the chimera was a thrombolytic agent with anticoagulant activity and thrombus-ditargeting with the activated-platelet membrane binding and fibrin clot binding activity. Compared to urokinase, the chimera had less reperfusion time, higher reperfusion ratio, and less bleeding effects on coronary thrombolysis by clot lysis assay in dogs. Thus, the chimera appeared to be suitable for thrombolytic therapy of thrombus diseases.
Ding
Fei-Xiang
FX
Department of Medical Genetics, The Second Military Medical University, Xiangyin Road 800, Shanghai 200433, China.
Yan
Hong-Li
HL
Lu
Yi-Ming
YM
Xue
Geng
G
Mei
Qian
Q
Huang
Jing-Jing
JJ
Zhao
Zhuan-You
ZY
Wang
Yu-Zhao
YZ
Sun
Shu-Han
SH
D000818:Animals; D017302:Annexins / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*; D001777:Blood Coagulation / Q000187:drug effects; D003001:Cloning, Molecular / Q000379:methods; D003328:Coronary Thrombosis / Q000188:drug therapy* / Q000473:pathology; D004285:Dogs; D005340:Fibrinogen / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*; D005343:Fibrinolytic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015801:Helminth Proteins / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*
D017302:Annexins; D005343:Fibrinolytic Agents; D015801:Helminth Proteins; D010455:Peptides; D011993:Recombinant Fusion Proteins; C449006:annexin B1, Taenia solium; D005340:Fibrinogen; D014568:Urokinase-Type Plasminogen Activator