rtrail (TNT related apoptosis-inducing ligand) mutant-mpeg-mal conjugate and application thereof

A technology of maleimide couples and maleimides, which is applied in the field of rTRAIL mutant-monomethylated polyethylene glycol maleimide conjugates, can solve the problems of TRAIL activity being greatly affected, Achieve the effects of easy quality control, long half-life, and no hidden dangers of liver toxicity

Active Publication Date: 2014-12-31
ZHEJIANG UNIV
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  • Abstract
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Problems solved by technology

The disadvantages of this conjugate are: First, LZ-TRAIL has hepatotoxicity according to literature reports, although studies on PEG-HZ-TRAIL have shown that it can improve the hepatotoxicity of LZ-TRAIL, this is always a hidden danger; Secondly, PEG-HZ-TRAIL only retains about 7.3% of the activity of the original TRAIL, indicating that this PEG modification method has a greater impact on the activity of TRAIL; finally, the coupling of PEG-HZ-TRAIL takes 12 hours

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  • rtrail (TNT related apoptosis-inducing ligand) mutant-mpeg-mal conjugate and application thereof
  • rtrail (TNT related apoptosis-inducing ligand) mutant-mpeg-mal conjugate and application thereof
  • rtrail (TNT related apoptosis-inducing ligand) mutant-mpeg-mal conjugate and application thereof

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[0067] The present invention will be further described in detail below with reference to the drawings and specific embodiments.

[0068] 1. Establish a human prostate cDNA library

[0069] (1) Extract human prostate total mRNA

[0070] Grind small pieces of frozen human prostate tissue (about 100 mg) with liquid nitrogen into powder, add 1 mL of TRIZOL reagent to continue grinding, transfer to 1.5 mL RNase-free EP tube, place at room temperature for 5 minutes, add 0.2 mL of chloroform and shake vigorously for 15 seconds. Place at room temperature for 3 minutes; centrifuge at 12000g for 15 minutes at 4°C, transfer the upper aqueous phase to another RNase-free EP tube; add 0.5 mL of isopropanol, place at room temperature for 10 minutes to precipitate RNA; centrifuge at 12000g for 10 minutes at 4°C, remove the supernatant, 75 Wash the precipitate with% ethanol; centrifuge at 12000g for 5 min at 4°C, remove the supernatant, dissolve it with 50μL DEPC water after drying, and store at -70...

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Abstract

The invention discloses an rTRAIL (TNT Related Apoptosis-Inducing Ligand) mutant-mPEG-MAL conjugate and an application thereof. The rTRAIL mutant-mPEG-MAL conjugate is formed in such a manner that mPEG-MAL is conjugated with the tripolymer of the rTRAIL mutant, wherein the amino acid sequence of the TRAIL mutant is shown in SEQ ID No.1; the molecular weight of the mPEG-MAL is 3000-10,000 Da. The application of the rTRAIL mutant-mPEG-MAL conjugate refers to that the conjugate is used for preparing antineoplastic drugs. Compared with the prior art, the rTRAIL mutant-mPEG-MAL conjugate has the advantages as follows: the mass is easy to control; the half life period is longer; the stability and the bioavailability are higher; 20% of apoptosis-inducting activity, of the original TRAIL molecule, to tumor cells are reserved, so that the druggability is higher; the response time for preparing the rTRAIL mutant-mPEG-MAL conjugate is shorter; the yield of the goal product is higher; hepatotoxicity potential hazards are eliminated.

Description

Technical field [0001] The invention belongs to the field of biotechnology and medicine, and specifically relates to an rTRAIL mutant-monomethylated polyethylene glycol maleimide conjugate and its application. Background technique [0002] Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is the third apoptotic factor of the TNF family discovered after TNF and FasL. It is a promising anti-cancer application prospect Biological drugs. TRAIL was cloned from the myocardial cDNA library by Wiley et al. It is named because its amino acid sequence has the structural characteristics of the TNF superfamily and can induce apoptosis in Jurkat cells and human lymphocytes transformed by EB virus. Many pre-clinical studies have shown that TRAIL can effectively induce apoptosis in a variety of cancer cell lines, while protecting normal cells from cytotoxic side effects. At present, phase I and II clinical trials on TRAIL and its receptor agonist antibodies have been condu...

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K14/525C07K1/107A61K38/19A61K47/48A61P35/00
Inventor 陈枢青潘利强
Owner ZHEJIANG UNIV
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