Unlock instant, AI-driven research and patent intelligence for your innovation.

Hydrophobic group-modified carboxy-terminal polyamidoamine dendrimers and its preparation method and its application in inhibiting the aggregation of β-amyloid protein

A terminal polyamidoamine tree and amyloid technology, which can be used in nervous system diseases, drug combinations, etc., can solve the problems of slow aggregation, high cytotoxicity, and little reference for Alzheimer's disease treatment, and achieve good biological Compatibility, good biocompatibility, reducing the effect of Aβ42 cytotoxicity

Inactive Publication Date: 2021-01-22
TIANJIN UNIV
View PDF7 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] Regarding the effects of various PAMAMs on Aβ, only amino-terminal PAMAMs have been reported to slow down the aggregation of Aβ1-28 (Biochem.Bioph.Res.Co 2006,339,577-58; Biochem.Bioph.Res.Co 2006,345,21 -28; NewJ.Chem.2012,36,211-216), but Aβ1-28 is only a hydrophobic sequence of Aβ40, which aggregates slowly and has no cytotoxicity under physiological conditions (New J.Chem.2012,36,211-216), in addition The cytotoxicity of amino-terminal PAMAM is relatively high, so the effect of amino-terminal PAMAM on Aβ1-28 has little significance for the treatment of Alzheimer's disease

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Hydrophobic group-modified carboxy-terminal polyamidoamine dendrimers and its preparation method and its application in inhibiting the aggregation of β-amyloid protein
  • Hydrophobic group-modified carboxy-terminal polyamidoamine dendrimers and its preparation method and its application in inhibiting the aggregation of β-amyloid protein
  • Hydrophobic group-modified carboxy-terminal polyamidoamine dendrimers and its preparation method and its application in inhibiting the aggregation of β-amyloid protein

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Example 1: Synthesis and characterization of hydrophobic group-modified PAMAM-COOH with a molar ratio of PEA to PAMAM-COOH of 40.

[0046] Weigh 120 mg of solid PAMAM-COOH and dissolve it in 30 mL of water, add 27.9 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride under stirring at 120 rpm at 25°C, activate for 15 minutes and then add 21 μL of PEA, and continue to stir for 17h to complete the reaction. The reaction solution was put into a dialysis bag with a molecular weight cut-off of 7kDa for dialysis to remove excess reactants and catalysts, and the dialysis solution was replaced every 4 hours: deionized water, dialysis for 7 days, and the obtained solution was concentrated by freeze-drying to obtain Phe- PAMAM-COOH-1 solid sample.

Embodiment 2

[0047] Example 2: Synthesis and characterization of hydrophobic group-modified PAMAM-COOH with a molar ratio of PEA to PAMAM-COOH of 85.

[0048] Weigh 120 mg of solid PAMAM-COOH and dissolve it in 20 mL of water, add 55.5 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride under stirring at 130 rpm at 30°C, activate for 20 minutes and then add 42μL of PEA, continue to stir for 20h to complete the reaction. The reaction solution was put into a dialysis bag with a molecular weight cut-off of 7kDa for dialysis to remove excess reactants and catalysts, and the dialysate was replaced every 5 hours: deionized water, dialyzed for 8 days, and the obtained solution was concentrated by freeze-drying to obtain Phe- PAMAM-COOH-2 solid sample.

Embodiment 3

[0049] Example 3: Synthesis and characterization of hydrophobic group-modified PAMAM-COOH with a molar ratio of PEA to PAMAM-COOH of 125.

[0050] Weigh 120 mg of solid PAMAM-COOH and dissolve it in 15 mL of water, add 83.4 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride under stirring at 150 rpm at 35°C, activate for 25 minutes and then add 69 μL of PEA, and continue to stir for 22 hours to complete the reaction. Put the reaction solution into a dialysis bag with a molecular weight cut-off of 7kDa for dialysis, remove excess reactants and catalysts, and replace the dialysis solution every 6h: deionized water, dialysis for 9 days, and the resulting solution is concentrated by freeze-drying to obtain Phe-PAMAM-COOH-3 solid sample.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
concentrationaaaaaaaaaa
Login to View More

Abstract

The invention relates to synthesis of a carboxyl terminal polyamide dendrimer with a terminal modified with a hydrophobic group and application of the carboxyl terminal polyamide dendrimer in inhibiting the aggregation of beta amyloid proteins. The carboxyl terminal polyamide dendrimer is a product obtained through the reaction of partial carboxyl at the terminal of a 5-generation carboxyl terminal polyamide dendrimer and a reactant ethylamine with a hydrophobic group, and the hydrophobic group substitution degree is 7.2%-42.3%. The synthesized carboxyl terminal polyamide dendrimer with the terminal with the hydrophobic group and carboxyl has the effects of inhibiting the aggregation of Abeta42 and reducing the cytotoxicity of a beta-amyloid protein aggregate, and the effects are not reported in the research of other types of polyamide dendrimers. The synthesized carboxyl terminal polyamide dendrimer has good biocompatibility and has wide development prospects as the drugs for treatingdiseases such as related diseases of the aggregation of the beta-amyloid proteins and Alzheimer's disease.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and relates to the synthesis of a 5th-generation carboxy-terminal polyamidoamine dendrimer whose surface is modified by hydrophobic groups and its application in inhibiting amyloid beta aggregation. Background technique [0002] Alzheimer's disease (AD) is a degenerative disease of the nervous system (Nature 2014, 507, 448-454), the most important type of dementia, accounting for 60-70% of dementia cases. The main symptom of AD patients is the loss of mobility in the later stage of the decline of intelligence and memory, which brings a huge economic burden to the society. At present, there are about 50 million AD patients in the world, and this number is still growing (ACS chemical neuroscience 2014, 5, 718-730). Although researchers have invested a lot of energy and money in the development of AD drugs, the existing drugs are only It can alleviate AD symptoms, but cannot cure AD (Cell 2005,...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C08G73/02A61P25/28
CPCA61P25/28C08G73/028
Inventor 孙彦王梓源余林玲董晓燕
Owner TIANJIN UNIV