Construction and characterization of novel staphylokinase variants with antiplatelet aggregation activity and reduced immunogenecity

Huabo Su, Yu Gao Zhang, Jin Tian He, Wei Mo, Yan Ling Zhang, Xian Mei Tao, Hou Yan Song

Research output: Contribution to journalArticle

14 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)336-342
Number of pages7
JournalActa Biochimica et Biophysica Sinica
Volume36
Issue number5
StatePublished - May 1 2004
Externally publishedYes

Fingerprint

Agglomeration
Fibrinolytic Agents
Ion Exchange Chromatography
Platelets
Chromatography
Platelet Aggregation
Gene expression
Escherichia coli
Gel Chromatography
Ion exchange
Guinea Pigs
Gels
Gene Expression
Kinetics
Antibodies
Staphylococcus aureus auR protein
Proteins

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 journalArticle

Su, Huabo ; Zhang, Yu Gao ; He, Jin Tian ; Mo, Wei ; Zhang, Yan Ling ; Tao, Xian Mei ; Song, Hou Yan. / Construction and characterization of novel staphylokinase variants with antiplatelet aggregation activity and reduced immunogenecity. In: Acta Biochimica et Biophysica Sinica. 2004 ; Vol. 36, No. 5. pp. 336-342.
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