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Method for synthesizing polypeptide in presence of ammonia-base rare earth catalyst

A rare earth catalyst and catalyst technology, which are applied in the field of catalyzing synthesis of polypeptides with amino rare earth catalysts, can solve the problems of complex operation, low molecular weight and low reaction activity, and achieve the effect of high activity

Inactive Publication Date: 2010-12-08
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The defect of this system is that the final product contains nickel metal, which affects its biological application (Nature, 1997, 390, 386-387); 2) In 2003, Schlaad et al reported a controllable NCA ring-opening polymerization method , using primary amine hydrochloride as a macroinitiator to catalyze the synthesis of polypeptides, the molecular weight distribution of the resulting product is very narrow, only 1.03, but the system’s reactivity is not high, and the monomers cannot react completely (Chem.Commun, 2003, 2944 -2945); 3) In 2004, people such as N.Hadjichristidis of Greece realized the living polymerization of NCA with traditional primary amines as initiators under high vacuum conditions, but this system requires very high purity of NCA monomers. Moreover, high vacuum conditions are not easy to realize, and the operation is also very complicated (Biomacromolecules, 2004, 5, 1653-1656); 4) In 2007, J.Cheng et al. developed a bistrimethylsilazane (HMDS) catalytic system, and the product molecular weight Controllable, narrow molecular weight distribution (1.19<PDI<1.26), high yield, almost 100%, see J.Am.Chem.Soc.2007, 129, 14114-14115; 5) 2008, C.Lin et al. Using [bis(diphenylethane)][N-(2-amino-1,2-diphenylethyl)-4-methylbenzenesulfonamide]platinum complex ((deep)Pt(MBS- NH)) as a catalyst can effectively initiate the ring-opening polymerization of lysine NCA, and the molecular weight of the obtained polypeptide is controllable and the molecular weight distribution is narrow. Body (Macromolecules, 2008, 41, 3455-3459)
So far, there is no report on the ring-opening polymerization of amino acid NCA monomer catalyzed by amino rare earth compounds

Method used

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Embodiment 1

[0016] A method for catalyzing the synthesis of polypeptides with amino rare earth catalysts, using three (bistrimethylsilylamino) rare earth metal compounds as catalysts to catalyze the ring-opening polymerization of glutamic acid-γ-benzyl ester-N-carboxy anhydride monomers, The molar ratio of the catalyst to the monomer is 1:200, the reaction temperature is 40° C., the reaction time is 2 days, the solvent is N, N-dimethylformamide, and the monomer concentration is 0.5 mol / L; three ( The rare earth metal element in the bis(trimethylsilylamino) rare earth metal compound is Sc, the yield of the synthetic polypeptide is 99%, the molecular weight is 38,000, and the molecular weight distribution is 1.2.

Embodiment 2

[0018] A method for catalyzing the synthesis of polypeptides with amino rare earth catalysts, using three (bistrimethylsilylamino) rare earth metal compounds as catalysts to catalyze the ring-opening polymerization of glutamic acid-γ-benzyl ester-N-carboxy anhydride monomers, The molar ratio of the catalyst to the monomer is 1:1200, the reaction temperature is 60° C., the reaction time is 2 days, the solvent is N, N-dimethylformamide, and the monomer concentration is 0.5 mol / L; three ( The rare earth metal element in the bis(trimethylsilylamino) rare earth metal compound is Y, and the yield of the synthetic polypeptide is 96%, and the molecular weight is 80,000

Embodiment 3

[0020] A method for catalyzing the synthesis of polypeptides with amino rare earth catalysts, using three (bistrimethylsilylamino) rare earth metal compounds as catalysts to catalyze the ring-opening polymerization of glutamic acid-γ-benzyl ester-N-carboxy anhydride monomers, The molar ratio of the catalyst to the monomer is 1:200, the reaction temperature is 40° C., the reaction time is 1 day, the solvent is N,N-dimethylformamide, and the monomer concentration is 0.5 mol / L tri(bis The rare earth metal element in the trimethylsilylamino) rare earth metal compound is La, the yield of the synthetic polypeptide is 94%, and the molecular weight is 28,000.

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Abstract

The invention discloses a method for synthesizing polypeptide in the presence of ammonia-base rare earth catalyst, which is characterized in that: tri(bis(trimethylsilyl)) rare earth metal compound is used as a catalyst to catalyze the ring-opening polymerization of a benzyl-gama-glutamate-N-carboxylic anhydride monomer to synthesize the polypeptide of which the molecular weight is 18,000 to 80,000, wherein the molar ratio of the catalyst to the monomer is 1:80 to 1:1,200; the reaction temperature is 0 to 60 DEG C; the reaction time is 1 to 3 days; a solvent is N,N-dimethylformamide; and the concentration of the monomer is 0.5mol / L. Compared with the prior art, the method has the advantages that: the used catalyst is cheap and easy to prepare and has high catalytic activity; and the molecular weight of the prepared polypeptide is controllable and the molecular distribution of the prepared polypeptide is narrow.

Description

technical field [0001] The invention relates to a method for synthesizing a polypeptide, in particular to a method for catalyzing the synthesis of a polypeptide with an amino rare earth catalyst. technical background [0002] Polypeptide is a kind of low toxicity, good biocompatibility, biodegradable polymer material, which is widely used in the research of biomedical field. Polypeptides can be made from natural amino acids, with rich sources of raw materials, and can be absorbed by the body after degradation in the body without causing inflammation. It is an ideal biological material. Compared with conventional polymer materials, polypeptides can form stable secondary structures such as α-helices and β-sheets. This self-assembly ability makes them have great prospects for biomedical and pharmaceutical applications, especially in medical fields such as drugs Controlled release, tissue engineering, biosensing and other aspects have its unique role. [0003] There are three ...

Claims

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Application Information

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IPC IPC(8): C08G69/16
Inventor 凌君彭慧陶鑫峰沈之荃
Owner ZHEJIANG UNIV
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