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Enzyme degradation-controllable anti-nonspecific protein adsorption polypeptide and monomer and preparation method thereof

A technology of monomers and inhibitors, applied in the field of peptides and their preparation, can solve the problems of large impact on the size of biomolecules, abnormal cell death, loss of protein non-adsorption, etc., achieve broad application prospects, and improve resistance to non-specific proteins The effect of adsorption capacity

Pending Publication Date: 2017-04-19
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Existing anti-nonspecific protein adsorption materials are mainly represented by polyethylene glycol (PEG), but polyethylene glycol has its obvious defects, including: 1) PEG will naturally decompose in the presence of oxygen and transition metal ions. Oxidation, the terminal hydroxyl group will be oxidized to aldehyde by the alcohol dehydrogenase in the body, and the aldehyde group can easily react with proteins or other molecules containing amino groups
2) The protein non-adsorption of PEG has certain requirements for molecular arrangement, too tight / or large molecular weight will lose the protein non-adsorption
3) The hydraulic radius of PEG molecules is large, and its apparent volume is about 5 to 10 times the molecular volume of water-soluble proteins of similar molecular weight, which has a great influence on the volume of modified biomolecules
4) After PEG is fixed to one end of the molecule, the functionalization of the other end also brings great difficulties
[0005] However, both polyethylene glycol and zwitterionic polymers have an important defect in the living body, especially in the human body, that is, they cannot enter the normal metabolic pathway of the human body, and are eliminated from the cells and the body through degradation, which often leads to cell breakdown. Unnatural death and inflammation in the body

Method used

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  • Enzyme degradation-controllable anti-nonspecific protein adsorption polypeptide and monomer and preparation method thereof
  • Enzyme degradation-controllable anti-nonspecific protein adsorption polypeptide and monomer and preparation method thereof
  • Enzyme degradation-controllable anti-nonspecific protein adsorption polypeptide and monomer and preparation method thereof

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preparation example Construction

[0072] The following exemplifies the preparation method of the anti-non-specific protein adsorption polypeptide with controllable enzymatic degradation of the present invention, preferably including the following parts:

[0073] (1) Condensation synthesis of dipeptide monomers with side chain protection

[0074] Through the condensation of glutamic acid and lysine with different protecting groups, such as γ-benzyl-N-tert-butoxycarbonyl-L-glutamic acid and N ε -Condensation of benzyloxycarbonyl-α-tert-butyl-L-lysine, and through selective deprotection, a dipeptide with side chains protected by benzyl and benzyloxycarbonyl was obtained, and purified by separation and used for The next step of polycondensation. The advantage of this method is that it can avoid directly protecting amino acids with two side chains (eg, γ-benzyl-L-glutamic acid and N ε -benzyloxycarbonyl--L-lysine) polycondensation after mixing produces the problem of uneven distribution of positively and negative...

Embodiment 1

[0090] 1) polycondensation

[0091] Take the first monomer (structural formula shown in formula I) 200mg (0.4mmol), then add 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC.HCl) 115mg ( 0.6mmol) and 1-hydroxybenzotriazole (HOBt) 81mg (0.6mmol). After adding 2 mL of anhydrous N, N-diformamide (DMF) to the system, seal it with a rubber stopper, bubble it with nitrogen for 30 min, and then react in a closed room at room temperature for 48 h. After the reaction, about 18 mL of anhydrous ether was added to the reaction system for precipitation. After standing still for about 20 minutes, the solvent was poured off to obtain an oily non-deprotected zwitterionic polypeptide with alternating glutamic acid and lysine residues.

[0092] 2) deprotection group

[0093] After completely dissolving the above oil with about 2mL of trifluoroacetic acid (TFA), add about 2mL of 33% (33wt.%) hydrobromic acetic acid (HBr / HOAc) solution for deprotection, and the reaction system wi...

Embodiment 2

[0097] 1) polycondensation

[0098] Take the first monomer (its structural formula is shown in formula I) 100mg (0.2mmol) and the second monomer (its structural formula is shown in formula III) 20mg (0.04mmol), add 1-ethyl-(3-dimethyl Aminopropyl) carbodiimide hydrochloride (EDC.HCl) (86.4mg, 0.45mmol) and 1-hydroxy-7-azobenzotriazole (HOAt) (61.3mg, 0.45mmol), and 0.004 mmol of cysteine ​​protected by aminobenzyloxycarbonyl group protected by end-capping agent. After adding about 2 mL of anhydrous DMF to the system, seal it with a rubber stopper, bubble it with nitrogen for 30 minutes, and then react in a closed room at room temperature for 24 hours. After the reaction is over, add about 18 mL of anhydrous ether to the reaction system for precipitation. After standing still for about 20 minutes, pour off the solvent to obtain an oily undeprotected polypeptide (the molar ratio of the first monomer to the second monomer is 5: 1).

[0099] 2) deprotection group

[0100] Afte...

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Abstract

The invention discloses enzyme degradation-controllable anti-nonspecific protein adsorption polypeptide and a monomer and a preparation method thereof. By means of polycondensation of a dipeptide monomer containing protected carboxyl group and protected amino group at the side chain and subsequent deprotection, polypeptide with perfect repetitive positive and negative charges is prepared, and anti-nonspecific protein adsorption capacity of polypeptide is enhanced. Further, by polycondensation of a dipeptide monomer containing protected carboxyl group and protected amino group at the side chain and an amino acid monomer modified with protected carboxyl group and protected amino molecules simultaneously contained at the side chain at different ratios and subsequent deprotection, anti-nonspecific protein adsorption polypeptide with different enzyme degradation half-life is obtained, and regulation and control of enzyme degradation capability of the anti-nonspecific protein adsorption polypeptide is realized. By controlling the ratio of an end-capping reagent to a monomer, molecular weight of the target polypeptide is regulated and controlled. By the utilization of functional modification groups on the end-capping reagent, modification of different proteins, polypeptide and other polymer and different material surfaces can be realized.

Description

technical field [0001] The invention relates to a polypeptide and a preparation method thereof, in particular to an anti-nonspecific protein adsorption polypeptide and a preparation method thereof. Background technique [0002] Anti-non-specific protein adsorption materials (nonfouling materials) is a special class of biocompatible materials proposed in the last ten years, and was listed as an annu.rev.biomed.eng. A new generation of biocompatible materials. By interacting with water, it prevents the adsorption of protein molecules, thereby avoiding further biochemical reactions, such as blood coagulation in blood and other problems. Through continuous and in-depth research on non-specific protein adsorption materials, it is found that anti-non-specific protein adsorption materials can not only effectively prevent the coagulation process in the blood contact system, but also can be applied to prevent the adsorption process of biological macromolecules at a wide range of sol...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K5/072C07K7/02C07K5/037C07C269/06C07C271/22
CPCC07K5/06104C07C269/06C07C271/22C07K5/0215C07K5/06113C07K7/02
Inventor 陈圣福杨庆华孙静泽郭雨濛
Owner ZHEJIANG UNIV
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