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Amphiphilic oligopeptide structure substance

An amphiphilic and oligopeptide technology, applied in the field of biomedicine, can solve the problem of not being able to obtain compounds or polymers, and achieve the effect of improving biological activity and increasing intake

Active Publication Date: 2021-08-06
WUHAN ZEZHI BIOLOGICAL PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The invention is to extract the two components separately, but the compounds or polymers of the two components cannot be obtained

Method used

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  • Amphiphilic oligopeptide structure substance
  • Amphiphilic oligopeptide structure substance
  • Amphiphilic oligopeptide structure substance

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Embodiment 1, synthesis (LLHH) n oligopeptide:

[0048] In the present invention, according to the structural characteristics of the cell inclusion body and the understanding of the mechanism of drug escape from the inclusion body, a kind of leucine-leucine-histidine was obtained by designing and screening by Fmoc polypeptide solid-phase synthesis technology -The basic sequence of histidine (LLHH) is the amphipathic oligopeptide structure of the mother nucleus sequence, in which the molecular structural formula of leucine (Leucine, Leu, L) is figure 1 ; The molecular structural formula of histidine (Histidine, His, H) is figure 2 ; Leucine-leucine-histidine-histidine (LLHH) basic sequence composition of the mother core sequence is image 3 ;Based on the mother nucleus sequence, the polymer leucine-leucine-histidine-histidine oligopeptide structure ((LLHH)n, where n is 1, 2, 3, 4, 5, 6, 7, 8 or 9; the structure of the 3-mer leucine-leucine-histidine-histidine ((LLHH)3...

Embodiment 2

[0049] Example 2. Construction of a tumor-targeted nucleic acid delivery system cRGD-R9-(LLHH)n / siRNA:

[0050] Integrin αvβ3 receptors are only expressed on tumor neovascular endothelial cell membranes and some tumor cell membranes, and are commonly used delivery targets for the study of small nucleic acid (siRNA) and other drugs for targeted therapy of tumors; oligopeptide cRGD is a specific ligand for αvβ3 receptors Studies have found that cRGD can target drug molecules such as small nucleic acid (siRNA) carried by non-chemical bond encapsulation or chemical bond coupling into tumor cells expressing αvβ3 receptors, so as to achieve the purpose of drug killing tumor cells (Park J, Singha K, Son S, Kim J, Namgung R, Yun C O, Kim W J. A review of RGD-functionalized nonviral gene delivery vectors for cancer therapy[J]. CancerGene Ther,2012,19(11):741-748. ).

[0051] In order to increase the number of drugs escaping into the cytoplasm in the cRGD-mediated drug delivery system ...

Embodiment 3

[0052] Embodiment 3, obtain siRNA sequence:

[0053] The siRNA EGFR sequence (siEGFR) was designed and obtained by using bioinformatics technology, and the glioblastoma cell line U87MG was used as a model cell, and the expression of the candidate siRNA sequence to silence the target gene EGFR mRNA was detected by RT-qPCR method, and the best activity was obtained. siEGFR sequence. Liposome transfection of 100 nM siEGFR, after 48 hours, the efficiency of silencing EGFR mRNA in U87 cells was as high as more than 85%, and was used as a model molecule of the present invention for testing cRGD-R9-(LLHH containing (LLHH)n structure ) n / siRNA gene silencing efficiency.

[0054] Negative control siNC sense strand sequence (5'-3') is: CGUGAUUGCGAGACUCUGAdTdT;

[0055] The sequence of the antisense strand (5'-3') is: UCAGAGUCUCGCAAUCACGdTdT.

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Abstract

The invention discloses an amphiphilic oligopeptide structure substance. The amphiphilic oligopeptide structure substance is characterized in that a leucine-leucine-histidine-histidine (LLHH) basic sequence is used as a parent nucleus sequence, the formed oligopeptide structure is (LLHH) n, and n is one of 1-9. A cRGD-R9-(LLHH)n / siEGFR self-assembled nano drug delivery system which is prepared by mixing at weight ratio t of 1:1, 5:1, 10:1, 20:1, 40:1 is optimized. An amphoteric oligopeptide structure and other components form a conjugate through chemical bonds and then the conjugate is used as the drug delivery system, so that the intake of drug molecules carried by the drug delivery system into cells can be improved, the carried drug molecules are promoted to escape from inclusion and enter into cytoplasm, and the biological activity of the drug molecules is improved.

Description

technical field [0001] The invention belongs to a technique for improving the biological activity of drug molecules in the field of biomedicine. Background technique [0002] Bis(2,4-dinitrophenyl)-L-histidine is a chemical substance with the formula C18H13N7O10. [0003] The premise of realizing the curative effect of drug molecules such as peptides, proteins, nucleic acids or compounds on intracellular targets is that a suitable drug delivery system carries these drug molecules into the cell first by relying on the endocytic pathway as the main uptake mechanism, and then from the inside of the cell. Inclusion bodies (Endosomes, or endosomes) are released into the cytoplasm during the process of transport to lysosomes before degradation, and only when they act on the target can they exert curative effect; otherwise, these drugs will either degrade or be excreted out of the cell and lose their curative effect. Conversely, if the curative effect of these drug molecules is to...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K5/103C07K7/06C07K7/08C07K14/00C07K19/00A61K47/64A61K47/69A61K31/7088A61P35/00
CPCC07K5/101C07K7/06C07K7/08C07K14/00C12N15/111A61K47/64A61K47/6929A61K31/7088A61P35/00C07K2319/33C12N2320/32C12N2310/14
Inventor 季爱民岑柏宏黎权辉陈佳扬陈漳浦
Owner WUHAN ZEZHI BIOLOGICAL PHARMA
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