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A kind of polypeptide inhibitor of interaction between mdm2 and p53 and application thereof
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A technology for MDM2 and cell inhibition, applied in the field of peptide inhibitors
Active Publication Date: 2020-08-11
ACADEMY OF MILITARY MEDICAL SCI
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The expression of p53 protein can promote the expression of MDM2 protein, but the overexpression of MDM2 protein will inhibit the expression and function of p53 protein, forming a negative feedback loop between the two
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Embodiment 1
[0056] Embodiment 1, discovery of polypeptide
[0057] Through a large number of sequence analysis and functional research, a polypeptide (derived from Zika virus) was screened out, as shown in sequence 1 of the sequence listing. According to molecular docking dynamics calculations, the polypeptide can bind to the binding site of the p53 protein of the MDM2 protein, and it can bind to the MDM2 protein intact for a long time ( figure 1 ), the interaction energy is strong, while other control polypeptides (such as LKRLPAGLLLGHGPIRMVLAILAF) cannot be combined with MDM2 protein intact ( figure 2 ). This shows that this polypeptide has a specific function, that is, it can have a strong and intact combination with MDM2 protein, so it prevents the combination of p53 protein and MDM2 protein, further promotes the accumulation of p53 protein in cells, and finally restores p53 protein The purpose of inhibiting the formation and growth of tumor cells.
Embodiment 2
[0058] Example 2, Functional Research of Polypeptides
[0059] The sequence of the experimental polypeptide is as follows: KKEAMEIIGGGGGGLAAMLRIINA (sequence 1 of the sequence listing).
[0060] The control polypeptide sequence is as follows: LKRLPAGLLLGHGPIRMVLAILAF.
[0061] The polypeptide to be tested is an experimental polypeptide or a control polypeptide.
[0062] 1. Peptides can effectively reduce the concentration of free MDM2 protein in U87 cells
[0063]1. Inoculate U87 cells into a 6-well plate (2×10 per well 6 cells), using DMEM medium containing 10% (volume percentage) fetal bovine serum, 100 U / ml penicillin and 100 μg / ml streptomycin, 5% CO 2 , 37 ℃ static culture for 24h.
[0064] 2. After completing step 1, take the 6-well plate, add the polypeptide to be tested so that the concentration in the system is 80 μM, 40 μM, 20 μM, 10 μM, 5 μM or 2.5 μM (3 replicate wells are set for each concentration; at the same time Set a blank control without adding the poly...
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Abstract
The invention discloses an MDM2 and p53 interaction polypeptide inhibitor and an application thereof. A protective polypeptide is as shown in a sequence 1 of a sequence table, is derived from Zika viruses and has functions of p53 protein-MDM2 protein interaction inhibitors, namely, the polypeptide can be effectively combined with MDM2 proteins in a biological body, the concentration of cancer suppressor proteins p53 in the body can be improved, formation or growth of tumor cells can be effectively inhibited by accumulation of more p53 proteins in the body, and finally, cancers are inhibited. The polypeptide inhibitor has great significance for tumor treatment.
Description
technical field [0001] The invention relates to a polypeptide inhibitor of the interaction between MDM2 and p53 and its application. Background technique [0002] Among various human diseases, the mortality rate caused by malignant tumors has always been at the forefront, and it is one of the most important diseases that endanger human health. Therefore, the formation mechanism of tumors, especially the research on the treatment of tumors has become a very important field of interdisciplinary fields such as biology, physics, chemistry and medicine. [0003] In human cancer, either the tumor suppressor gene p53 is mutated or completely deleted, and functional p53 protein cannot be synthesized, or the combination of MDM2 protein and p53 protein inhibits the activity of p53. Therefore, designing a drug molecule that can achieve the purpose of treating cancer by blocking the combination of MDM2 protein and p53 protein is a preferred way of cancer treatment at present. Such dru...
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