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pH-sensitive polypeptide and application thereof

A sensitive and polypeptide modification technology, applied to polypeptides, peptides, and hybrid peptides containing positioning/targeting motifs, can solve the problems of lack of specificity and limit the application of CPPs in vivo, so as to reduce absorption and increase active The effect of targeted effects

Active Publication Date: 2017-05-10
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although CPPs can effectively mediate the entry of exogenous biomacromolecules, the lack of specificity limits the in vivo application of CPPs

Method used

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  • pH-sensitive polypeptide and application thereof
  • pH-sensitive polypeptide and application thereof
  • pH-sensitive polypeptide and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Synthesis of HE-CPP-PEG-DSPE

[0047] Weigh 5.6mg Mal-PEG-DSPE (Fanshuo Biotechnology Co., Ltd., B06012) into a 1.5mL EP tube, add 1mL DMF to dissolve, add 9mg HE-CPP to dissolve and shake to make it evenly dispersed, adjust the pH with triethylamine to 7.0. The reaction tube was flushed with nitrogen to protect the seal, and the reaction was shaken at 37°C for 24h. Evaporate the organic solvent DMF on a rotary evaporator, place in a desiccator to vacuum for 4 hours, add 1.5 mL of aqueous solution to hydrate, and freeze-dry for storage.

[0048] Equimolar concentrations of the products before and after the reaction were prepared respectively. Take a 96-well plate, add 100 μL of sample to each well, then add 100 μL of 1 mM DTNB solution, detect with a microplate reader at 450 nm, and calculate the reaction efficiency by detecting the residual amount of sulfhydryl groups by Ellman test. The yield of HE-CPP-PEG-DSPE was 55.04%.

[0049] Preparation of HE-CPP modified li...

Embodiment 2

[0053] Synthesis of CPP-PEG-DSPE

[0054] Weigh 5.6 mg of Mal-PEG-DSPE into a 1.5 mL EP tube, add 1 mL of DMF to dissolve, add 2.5 mg of R6 to dissolve and mix well, and the rest of the operations are the same as in Example 1.

[0055] The synthesis yield was detected by the method of Example 1, and the yield of CPP-PEG-DSPE was 89.62%.

[0056] Preparation of CPP-modified liposomes

[0057] Weigh 120mg of SPC, 20mg of CH, 10.46mg of CPP-PEG-DSPE and completely dissolve in chloroform, transfer to a 250mL eggplant-shaped bottle, rotate and evaporate chloroform at 40°C, spread a uniform monolayer film, and place in a desiccator vacuum overnight. Add 5 mL of distilled water to hydrate the lipid monolayer membrane, shake it to make it into a primary liposome, sonicate the probe for 5 minutes, 200W, and pass the prepared blue opalescent solution through a 0.22 μm filter membrane to obtain CPP modified with uniform particle size liposomes, namely CPP-L. The particle size of the ...

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Abstract

The invention discloses a pH-sensitive polypeptide and an application thereof. The pH-sensitive polypeptide is formed by linking a peptide chain with reversibly-changed net charge to one end of a cell-penetrating peptide through a flexible peptide chain. The pH-sensitive polypeptide can selectively give play to pH sensitivity, and restore positive electrical property at an acidic environmental site to realize efficient cell uptake. The pH-sensitive polypeptide is linked to an amphiphilic block copolymer to synthetize a pH-sensitive peptide-modified amphiphilic block copolymer; then, a liposome which contains a lipid carrier material and the pH-sensitive peptide-modified amphiphilic block copolymer is prepared by a film dispersion method; the obtained liposome shows a targeting ability of tendency to affinity with acidic microenvironment sites (such as tumor, inflammation or infection sites, cell endosomes or lysosomal environments, and has important significance to targeted therapy.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a pH-sensitive polypeptide targeting an acidic environment and an application thereof. Background technique [0002] Cell-penetrating peptides (CPPs) are a class of small molecular polypeptides consisting of no more than 30 amino acid residues, which have strong transmembrane transport ability and biocompatibility. According to the difference in amino acid composition, Can be divided into cationic CPPs and amphiphilic CPPs. Although CPPs can effectively mediate the entry of exogenous biomacromolecules, the lack of specificity limits the in vivo application of CPPs. Based on the charge characteristics of cationic CPPs, environment-sensitive cell-penetrating peptides constructed by the strategy of "shielding first and then activating" have become a new research hotspot in recent years, especially for the acidic microenvironment existing in the human...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K19/00A61K9/127A61K47/42A61K47/30A61K31/337A61P35/00
CPCA61K9/127A61K31/337A61K47/30A61K47/42C07K5/06147C07K5/0823C07K5/1021C07K2319/10
Inventor 孙春萌涂家生余荧蓝
Owner CHINA PHARM UNIV
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