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A conjugate of trehalose derivatives and carbohydrate antigens and its preparation method and application

A technology of conjugates and derivatives, applied in the field of conjugates of trehalose derivatives and sugar antigens and its preparation, can solve the problems of unstable coupling rate, complex composition, and uncertain coupling sites of glycoprotein vaccines And other issues

Active Publication Date: 2021-12-17
GUANGZHOU UNIVERSITY OF CHINESE MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The classic strategy is to conjugate glycoantigens to carrier proteins to enhance their immunogenicity, but glycoprotein vaccines have disadvantages such as uncertain conjugation sites, unstable conjugation rates, and complex components.

Method used

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  • A conjugate of trehalose derivatives and carbohydrate antigens and its preparation method and application
  • A conjugate of trehalose derivatives and carbohydrate antigens and its preparation method and application
  • A conjugate of trehalose derivatives and carbohydrate antigens and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0065] Example 1 Preparation of Trehalose Derivatives and Carbohydrate Antigen Conjugates 1, 2, 3, 4 and L2-3

[0066] 1) Synthesis of Compound 5

[0067]

[0068] Trehalose (10.00g, 0.03mol) and p-toluenesulfonic acid monohydrate (1.10g, 5.84mol) were dissolved in dimethylformamide, and anisaldehyde dimethyl acetal (20mL, 0.117 mol), stirred at room temperature for reaction, after 24 hours of reaction, diluted with ethyl acetate, saturated sodium bicarbonate solution, left standing, a white solid was precipitated, filtered by suction to obtain compound 5 (11.90 g, 70%). 1 H NMR (400MHz, CD 3 OD)δ7.41-7.39(d, J=8.8Hz, 4H), 6.88-6.68(d, J=8.8Hz, 4H), 5.51(s, 2H, PhCH), 5.11(d, J=3.6Hz, 2H,H-1&H-1′),4.19(dt,J=10.0,4.8Hz,2H,H5&H5′),4.12-4.06(m,2H,H3&H3′),4.03-3.98(t,J=9.6,2H ,H4&H4′), 3.77(s, 6H), 3.72-3.67(t, J=10.4Hz, 2H), 3.61(dd, J 1 =9.2Hz,J 2 =4.0Hz, 2H), 3.45(t, J=9.6, 2H), 3.31-3.29(m, 2H); HR-ESI-MS(m / z): calcd for C 28 h 34 o 13 [M+H] + 579.2072 found, 579.2...

Embodiment 2

[0137] Example 2: ELISA immunoassay

[0138] (1) The prepared compounds 1 to 4 are respectively used as vaccine molecules 1, 2, 3 and 4, according to the vaccine molecule: distearoylphosphatidylcholine (DSPC): cholesterol = 1:6.5:5 dissolved in DCM -MeOH (1:1, v / v, 2mL) mixed solution, spin the solvent to form a thin layer of lipid film on the bottle wall. Add 2.0 mL of hydroxyethylpiperazine ethylsulfuric acid (HEPES) buffer solution (20 Mm, pH=7.5), and sonicate for 10-20 min to obtain liposomes 1, 2, 3 and 4.

[0139] (2) Immunization of mice: C57BL / 6 mice aged 6-8 weeks were divided into four groups, 6 mice in each group. The immunization test was carried out by subcutaneous injection in mice, and the scheme of one initial immunization and three booster immunizations was used to inject liposomes 1, 2, 3 and 4. Each injection volume is 0.1mL, and blood is collected on days 0, 27, 35, and 49. Blood is collected from each mouse at 0.1mL-0.2mL, placed at 4°C for half an hour...

Embodiment 3

[0143] Example 3: Antibody-Mediated Complementation-Dependent Cytotoxicity (CDC)

[0144] CT-26 cells (mouse colon cancer cells) in the logarithmic growth phase were digested with trypsin, and 1 × 10 4 Cells were seeded in 96-well plates, cultured overnight at 37°C, and washed twice with serum-free 1640 medium. Take the serum samples of 6 mice in the compound 1 group that were blood drawn on day 38, take 7 μl for each sample, then mix the serum samples of the 6 mice and dilute 50 times with serum-free 1640 medium to obtain mouse serum Diluent. The mouse serum dilutions of Compound 2, Group 3, Group 4 and the blank control group were prepared according to the above method. Group 1, Group 2, Group 3, Group 4, and the blank control group (pre-immune serum) were all provided with a sample maximum enzyme activity control group, a sample control group, and a sample treatment group. Six replicate holes were made in parallel for each group. 100 μl of diluted mouse serum solution wa...

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Abstract

The invention relates to the technical fields of chemistry and medicine, and discloses a conjugate of a trehalose derivative and a carbohydrate antigen, a preparation method and an application thereof. The conjugate of the present invention is obtained by coupling trehalose as an embedded adjuvant with a tumor-associated carbohydrate antigen (STn or Tn) abnormally expressed on the surface of tumor cells; it has the advantages of clear structure, simple and convenient synthesis method, stable and controllable product quality, etc. , especially the vaccine can overcome the disadvantage of weak immunogenicity of carbohydrate antigens, and induce the production of specific IgG antibodies with high affinity, so as to achieve the anti-tumor effect of targeting and killing tumor cells.

Description

technical field [0001] The invention relates to the technical fields of chemistry and medicine, in particular to a conjugate of a trehalose derivative and a carbohydrate antigen and a preparation method and application thereof. Background technique [0002] Nowadays, cancer has become the number one killer of human beings and the largest public health problem in the world. The mortality rate of malignant tumors shows a clear increase trend, which seriously threatens human life. The current methods of treating cancer include surgery, chemotherapy, radiotherapy, and immunotherapy, among which tumor immunotherapy is one of the hot spots in the study of tumor treatment. Tumor-associated carbohydrate antigens (TACAs), which are abnormally overexpressed in tumor cells, have important biological functions and are excellent targets for the design of carbohydrate antigen tumor vaccines. [0003] However, tumor-associated carbohydrate antigens (TACAs) are T cell-independent antigens ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07H15/26C07H1/00A61P35/00
CPCC07H15/26C07H1/00A61P35/00Y02P20/55
Inventor 廖国超刘中秋李文伟练庆海杨德盈吴鹏卢琳琳
Owner GUANGZHOU UNIVERSITY OF CHINESE MEDICINE
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