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Novel cross-linked molecule for protein targeted transportation as well as preparation method and application of novel cross-linked molecule

A protein target and application method technology, applied in the field of protein targeted transport, can solve the problems of high toxicity and low efficiency of protein transport system, and achieve the effects of reducing toxicity, improving water solubility and improving efficiency

Pending Publication Date: 2021-08-13
NANJING UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The technical problem to be solved by the present invention is to provide a novel cross-linking molecule for protein targeted transport and its preparation method and application, so as to solve the problems of low efficiency and high toxicity of protein transport system in the prior art

Method used

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  • Novel cross-linked molecule for protein targeted transportation as well as preparation method and application of novel cross-linked molecule
  • Novel cross-linked molecule for protein targeted transportation as well as preparation method and application of novel cross-linked molecule
  • Novel cross-linked molecule for protein targeted transportation as well as preparation method and application of novel cross-linked molecule

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] First, prepare a part (I-1) of the cross-linked molecule for protein targeted delivery, and the synthetic route is as follows:

[0050]

[0051] Specifically include the following steps:

[0052] (1) Dissolve 15.3g of compound 1' (78.77mmol) in 20ml of ultra-dry dichloromethane, add 4.4ml of triethylamine (31.66mmol) under ice bath, and react in ice bath for 30 minutes; then add 5g of p-toluenesulfonyl chloride ( 26.23mmol) was dissolved in 20ml of dichloromethane and slowly added to the above system (about 30 minutes), and reacted in ice bath for 1 hour; then turned to room temperature and reacted overnight. After TLC (petroleum ether: ethyl acetate = 1:4) monitors the completion of the reaction, then extracts and purifies the product through a silica gel column to obtain compound 2'. After testing, the weight of the compound 2' is 6.5029g, and the yield 71.2%;

[0053] (2) Dissolve 3.005g of compound 2' (8.62mmol) in 30ml of ultra-dry dimethylformamide, add 1.53g...

Embodiment 2

[0074] First, prepare a part of the cross-linked molecule (I-2) for protein targeted delivery, and the synthetic route is as follows:

[0075]

[0076] Specifically include the following steps:

[0077](1) Dissolve 15.3g of compound 1' (78.77mmol) in 20ml of ultra-dry dichloromethane, add 5.2ml of diisopropylethylamine (31.46mmol) under ice bath, and react in ice bath for 30 minutes; then add 5g of p-toluene Sulfonyl chloride (26.23 mmol) was dissolved in 20 ml of dichloromethane and slowly added to the above system (about 30 minutes), and reacted in ice bath for 1 hour; then turned to room temperature for overnight reaction. After TLC (petroleum ether: ethyl acetate = 1:4) monitors the completion of the reaction, then extracts and purifies the product through a silica gel column to obtain compound 2'. After testing, the weight of the compound 2' is 6.102g, and the yield 66.8%;

[0078] (2) Dissolve 3.005g of compound 2' (8.62mmol) in 30ml of ultra-dry dimethylformamide, ...

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Abstract

The invention discloses a novel cross-linked molecule for protein targeted transportation as well as a preparation method and application of the novel cross-linked molecule, and belongs to the technical field of protein targeted transportation. The novel cross-linked molecule contains a new cross-linked molecule comprising tetraethylene glycol serving as a fundamental chain and containing a cyclooctyne derivative group, a disulfide bond and an amido bond, and a molecule synthesized according to a reference document and containing a targeting group, a pH sensitive group and an azide group of a hydrophobic carbon chain. The preparation method of the novel cross-linked molecule comprises the following steps: firstly, deriving one end of tetraethylene glycol to be connected with a phthalimide structure, and connecting the other end of tetraethylene glycol to a sulfydryl structure; and then introducing a disulfide bond on a sulfydryl group, then hydrolyzing one end of the phthalimide to form primary amine, and then conducting combining with an activated molecule containing a cyclooctyne derivative. A novel carrier-free protein targeting transportation system can be prepared by crosslinking with protein and connecting with molecules containing structures such as targeting groups. The problems of low efficiency, high toxicity and the like of a protein transportation system can be solved.

Description

technical field [0001] The invention relates to the technical field of protein targeted transport, in particular to a novel cross-linking molecule for protein targeted transport and its preparation method and application. Background technique [0002] Proteins are essential players in a variety of cellular processes, and protein therapeutics deliver proteins into cells to replace dysfunctional proteins, providing an opportunity for drug development in a variety of diseases, including cancer, inflammation, and lysosomal storage diseases. a promising approach. Intracellular delivery of proteins also represents a useful strategy for cellular imaging and diagnostics, genome engineering, and synthetic biology. However, native proteins are mostly membrane impermeable and prone to degradation by proteolytic enzymes in cells, especially in lysosomes. Vector systems for efficient intracellular delivery of functional proteins are critical to advancing protein-based therapeutics. ...

Claims

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Application Information

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IPC IPC(8): C07D225/08C07C323/19C07C319/22C07K1/107
CPCC07D225/08C07C323/19C07K14/765C12N9/0065C12Y111/01006C07C2603/36
Inventor 王晓剑朱世玉李伟田宏妍王益万王保川
Owner NANJING UNIV OF TECH