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Double-functional molecule for dissolving thrombus and inhibiting blood platelet aggregate and use thereof

A platelet aggregation and bifunctional molecule technology, applied in the biological field, can solve the problems of difficult chemical cross-linking operation, increased cost, easy loss of activity, etc.

Inactive Publication Date: 2008-07-02
NORTHWEST A & F UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, chemical crosslinking has problems such as difficult operation, easy loss of activity, substantial increase in cost, and pollution to the environment.

Method used

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  • Double-functional molecule for dissolving thrombus and inhibiting blood platelet aggregate and use thereof
  • Double-functional molecule for dissolving thrombus and inhibiting blood platelet aggregate and use thereof
  • Double-functional molecule for dissolving thrombus and inhibiting blood platelet aggregate and use thereof

Examples

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Embodiment Construction

[0036] In the RGD bifunctional molecule for thrombolysis / inhibition of platelet aggregation of the present invention, the RGD coding sequence is fused to the wild-type Fibrolase gene when synthesizing the RGD-Fibrolase gene.

[0037] According to the structural characteristics and mode of action of Fibrolase, a dual-functional RGD-Fibrolase molecular structure with the ability to dissolve thrombus and inhibit platelet aggregation was designed, and produced by genetic engineering. new properties, and the preparation process is simple and safe.

[0038] From the three-dimensional structure of Fibrolase, amino acids 69-74 are located outside the molecular structure, presenting a prominent Loop shape, away from the known active center. The introduction of the RGD sequence at this position can not only make the RGD better play the anticoagulant function, but also have less impact on the activity of Fibrolase, and maintain the fibrolase fibrolytic activity well.

[0039] The RGD bi...

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Abstract

The invention discloses a thrombolytic / platelet aggregation inhibiting dual-function molecule and uses thereof. The thrombolytic / platelet aggregation inhibiting dual-function molecule is a mutant of Fibrolase (substitution of 69-74 amino acid sequence T(Thr)-S(Ser)-V(Val)-S(Ser)-H(His)-D(Asp) of Fibrolase with G(Gly)-P(Pro)-R(Arg)-G(Gly)-D(Asp)-W(Trp)-R(Arg)-M(Met)-L(Leu)-G(Gly)) containing a RGD sequence. The invention also discloses a preparation method. The inventive Fibrolase mutant can be used a novel thrombolytic drug, and has thrombolytic and platelet aggregation inhibiting functions.

Description

technical field [0001] The invention belongs to the field of biotechnology, and relates to a thrombolytic / inhibiting platelet aggregation bifunctional molecule and its application, specifically, to a thrombolytic / inhibiting platelet aggregation bifunctional molecule and its application, the thrombolytic / inhibiting platelet aggregation bifunctional molecule The functional molecule has applications in the preparation of drugs for inhibiting platelet aggregation and thrombolysis. Background technique [0002] Fibrolase is a zinc metalloprotease from the American southern copperhead (Agkistrodon contortrix contortrix), which has fibrinolytic activity and no hemorrhagic activity. It is a polypeptide chain composed of 203 amino acid residues, with a molecular weight of 23kD and a cyclized glutamate residue at the N-terminal. 1 mol of zinc atom is bound to 1 mol of Fibrolase protein, and the loss of zinc will lead to its rapid inactivation (Ahmed NK, et al....

Claims

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Application Information

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IPC IPC(8): C12N9/68C07K1/107A61K38/48A61P7/02
Inventor 郭蔼光张守涛
Owner NORTHWEST A & F UNIV
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