Anticoagulated blood polypeptides and uses thereof

An anticoagulant and application technology, applied in the field of anticoagulant polypeptide and its application, to achieve the effects of enhancing anticoagulant activity, inhibiting thrombin activity, and strong anticoagulant activity

Active Publication Date: 2009-02-25
INST OF BIOENG ACAD OF MILITARY MEDICAL SCI OF THE CHINESE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Current anticoagulants do not meet these requirements

Method used

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  • Anticoagulated blood polypeptides and uses thereof
  • Anticoagulated blood polypeptides and uses thereof
  • Anticoagulated blood polypeptides and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Example 1: Synthesis and purification of polypeptide 1

[0054] 1. Synthesis:

[0055] Weigh 0.17g Rink resin (0.1mmol, substitution rate 0.6g / mmol), the consumption of each Fmoc protected amino acid is 0.5mmol, with 1-hydroxybenzotriazole (HoBt) and dicyclohexylcarbodiimide (DCC, Acros company) as the condensing agent, piperidine (Piperidine, Shanghai Jill Biochemical) deprotection, according to the operating instructions of the ABI433A solid-phase synthesizer of Applied Systems Biosystems in the United States, appropriately prolong the coupling time (60-90min) and deprotection time (20- 30min), synthesize peptide-resin.

[0056] Take the above peptide-resin and put it into 10ml lysate (composition: 0.5g dimercaptothreitol (DTT), 0.5ml water, 8.8ml trifluoroacetic acid (TFA), 0.2ml triisopropylsilane (TIPS)) , lysed for 3.0 hours, filtered with a G3 glass sand core funnel, evaporated most of the filtrate with a rotary evaporator to about 2ml of residual liquid, then ...

Embodiment 2

[0070] Example 2: Synthesis and purification of polypeptide 2

[0071] 1. Synthesis:

[0072] Weigh 0.17g Rink resin (0.1mmol, substitution rate 0.6g / mmol), the consumption of each Fmoc protected amino acid is 0.5mmol, with 1-hydroxybenzotriazole (HoBt) and dicyclohexylcarbodiimide (DCC, Acros company) as the condensing agent, piperidine (Piperidine, Shanghai Jill Biochemical) deprotection, according to the operating instructions of the ABI433A solid-phase synthesizer of Applied Systems Biosystems in the United States, appropriately prolong the coupling time (60-90min) and deprotection time (20- 30min), synthesize peptide-resin.

[0073]Take the above peptide-resin and put it into 10ml lysate (composition: 0.5g dimercaptothreitol (DTT), 0.5ml water, 8.8ml trifluoroacetic acid (TFA), 0.2ml triisopropylsilane (TIPS)) , lysed for 3.0 hours, filtered with a G3 glass sand core funnel, evaporated most of the filtrate with a rotary evaporator to about 2ml of residual liquid, then p...

Embodiment 3

[0087] Example 3: Synthesis and purification of polypeptide 3

[0088] 1. Synthesis:

[0089] Weigh 0.17g Rink resin (0.1mmol, substitution rate 0.6g / mmol), the consumption of each Fmoc protected amino acid is 0.5mmol, with 1-hydroxybenzotriazole (HoBt) and dicyclohexylcarbodiimide (DCC, Acros company) as the condensing agent, piperidine (Piperidine, Shanghai Jill Biochemical) deprotection, according to the operating instructions of the ABI433A solid-phase synthesizer of Applied Systems Biosystems in the United States, appropriately prolong the coupling time (60-90min) and deprotection time (20- 30min), synthesize peptide-resin.

[0090] Take the above peptide-resin and put it into 10ml lysate (composition: 0.5g dimercaptothreitol (DTT), 0.5ml water, 8.8ml trifluoroacetic acid (TFA), 0.2ml triisopropylsilane (TIPS)) , lysed for 3.0 hours, filtered with a G3 glass sand core funnel, evaporated most of the filtrate with a rotary evaporator to about 2ml of residual liquid, then ...

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Abstract

The invention discloses an anticoagulant polypeptide, belonging to the field of biomedicine. The primary structure of the anticoagulant polypeptide is shown as the general formula: (D)-FPRP-X1-X2-X3-X4-X5-QGDFEPIPEDAYDE-NH2. The invention has the advantages that the invention designs and synthesizes one type of anticoagulant polypeptide according to the structure characteristics and action mode of thrombin and Bivalirudin which is anticoagulant drug, and the polypeptide can inhibit the activity of the thrombin efficiently and specifically; furthermore, the number of amino acid in the anticoagulant polypeptide is equal to that of the Bivalirudin, thus synthesis is easy, and the activity of anticoagulation is stronger.

Description

technical field [0001] The invention relates to a class of anticoagulant polypeptides and uses thereof, belonging to the field of biomedicine. Background technique [0002] Blood coagulation is an important physiological defense process of the body, but pathological thrombus seriously endangers human health. At present, the main anticoagulant drugs used clinically at home and abroad are unfractionated heparin, low molecular weight heparin, warfarin, etc. These drugs have the disadvantages of causing side effects such as thrombocytopenia and bleeding, or requiring close laboratory monitoring. Peptide anticoagulant drugs, such as hirudin, bivalirudin, and small-molecule peptide drugs (such as ximelagatran, etc.) The key development direction of blood medicine. [0003] Thrombin plays a central role in the thrombus process: (1) cleaves fibrinogen fibrin; (2) activates factors V, VIII and XI, which in turn form more thrombin; (3) stimulates platelets. In addition, fibrin cros...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/815C07K14/81C12N15/12A61K38/58A61K38/55A61P7/02
Inventor 戴秋云黄园园董铭心胡洁
Owner INST OF BIOENG ACAD OF MILITARY MEDICAL SCI OF THE CHINESE
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