Abstract
To develop target thrombolytic agents with fibrinolytic activity, antiplatelet aggregation activity and reduced immunogenicity, two staphylokinase variants containing Arg-Gly-Asp (RGD) motif were constructed. Gene expression was induced in E. coli JF1125 and the variants, designated DGR and RL1, were purified with gel filtration and ion-exchange chromatography and the purity was over 95%. The fibrinolytic activity and kinetic constants of the two variants were comparable to those of recombinant wild-type staphylokinase. Both the variants can inhibit the platelet aggregation at a final concentration of 2 μM. The titers of antibodies against variants were much lower than those against recombinant staphylokinase in guinea pigs, which indicated that the immunogenicity of the variants was greatly reduced. These results confirm that it is possible to design and produce a bifunctional protein that possesses fibrinolytic and antiplatelet aggregation activities.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 336-342 |
| Number of pages | 7 |
| Journal | Acta Biochimica et Biophysica Sinica |
| Volume | 36 |
| Issue number | 5 |
| State | Published - May 1 2004 |
| Externally published | Yes |
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Keywords
- Antiplatelet aggregation
- Immunogenicity
- RGD
- Staphylokinase
ASJC Scopus subject areas
- Biophysics
- Biochemistry
Cite this
Construction and characterization of novel staphylokinase variants with antiplatelet aggregation activity and reduced immunogenecity. / Su, Huabo; Zhang, Yu Gao; He, Jin Tian; Mo, Wei; Zhang, Yan Ling; Tao, Xian Mei; Song, Hou Yan.
In: Acta Biochimica et Biophysica Sinica, Vol. 36, No. 5, 01.05.2004, p. 336-342.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Construction and characterization of novel staphylokinase variants with antiplatelet aggregation activity and reduced immunogenecity
AU - Su, Huabo
AU - Zhang, Yu Gao
AU - He, Jin Tian
AU - Mo, Wei
AU - Zhang, Yan Ling
AU - Tao, Xian Mei
AU - Song, Hou Yan
PY - 2004/5/1
Y1 - 2004/5/1
N2 - To develop target thrombolytic agents with fibrinolytic activity, antiplatelet aggregation activity and reduced immunogenicity, two staphylokinase variants containing Arg-Gly-Asp (RGD) motif were constructed. Gene expression was induced in E. coli JF1125 and the variants, designated DGR and RL1, were purified with gel filtration and ion-exchange chromatography and the purity was over 95%. The fibrinolytic activity and kinetic constants of the two variants were comparable to those of recombinant wild-type staphylokinase. Both the variants can inhibit the platelet aggregation at a final concentration of 2 μM. The titers of antibodies against variants were much lower than those against recombinant staphylokinase in guinea pigs, which indicated that the immunogenicity of the variants was greatly reduced. These results confirm that it is possible to design and produce a bifunctional protein that possesses fibrinolytic and antiplatelet aggregation activities.
AB - To develop target thrombolytic agents with fibrinolytic activity, antiplatelet aggregation activity and reduced immunogenicity, two staphylokinase variants containing Arg-Gly-Asp (RGD) motif were constructed. Gene expression was induced in E. coli JF1125 and the variants, designated DGR and RL1, were purified with gel filtration and ion-exchange chromatography and the purity was over 95%. The fibrinolytic activity and kinetic constants of the two variants were comparable to those of recombinant wild-type staphylokinase. Both the variants can inhibit the platelet aggregation at a final concentration of 2 μM. The titers of antibodies against variants were much lower than those against recombinant staphylokinase in guinea pigs, which indicated that the immunogenicity of the variants was greatly reduced. These results confirm that it is possible to design and produce a bifunctional protein that possesses fibrinolytic and antiplatelet aggregation activities.
KW - Antiplatelet aggregation
KW - Immunogenicity
KW - RGD
KW - Staphylokinase
UR - http://www.scopus.com/inward/record.url?scp=4043060094&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4043060094&partnerID=8YFLogxK
M3 - Article
C2 - 15156275
AN - SCOPUS:4043060094
VL - 36
SP - 336
EP - 342
JO - Acta Biochimica et Biophysica Sinica
JF - Acta Biochimica et Biophysica Sinica
SN - 1672-9145
IS - 5
ER -