Polypeptide or derivatives thereof and application of polypeptide or derivatives thereof in preparation of medicines for preventing and treating tumors

A technology of derivatives and drugs, applied in anti-tumor drugs, drug combinations, peptides, etc., can solve the problem of low biological stability, and achieve the effects of less toxic and side effects, significant curative effect, and safe use

Inactive Publication Date: 2020-06-26
BEIJING WEIFENG YIMIN TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This patented technology allows researchers to study how proteins like histone acetyltransferase (HAT) are involved with regulating gene expression during cellular processes such as DNA replication, transcriptional activity, differentiation, apoptosis, angiogenesis, necrosis, inflammations, immune responses, metabolism, etc., which plays an important role in various biological functions including development, tissue repairing, blood vessel formation, wound healing, bacterial defense mechanisms against disease attacks, degenerated neurons, and drug discovery efforts towards developing new treatments aimed at prevention/treatment of certain types of brain disorders caused by abnormalities associated with specific genes called c-myc.

Problems solved by technology

The technical problem addressed by this patented technology relates to finding ways to specifically silence genetic material from cancerous tissue without causing damage other healthy organs like kidneys or blood vessels. This could lead to improved treatments against certain types of brain nerve disease.

Method used

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  • Polypeptide or derivatives thereof and application of polypeptide or derivatives thereof in preparation of medicines for preventing and treating tumors
  • Polypeptide or derivatives thereof and application of polypeptide or derivatives thereof in preparation of medicines for preventing and treating tumors
  • Polypeptide or derivatives thereof and application of polypeptide or derivatives thereof in preparation of medicines for preventing and treating tumors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] The synthesis of embodiment 1 polypeptide

[0027] For the amino acid sequence of the polypeptide CM4, refer to SEQ ID No.1 in the sequence listing. Peptide CM4 was synthesized and purified by China Peptide Biochemical Co., Ltd.

[0028] Two unnatural amino acids S-pentylalanine (S5) were introduced for solid-phase polypeptide chain synthesis. After the solid-phase polypeptide chain is synthesized, ruthenium is used as a catalyst to perform olefin metathesis reaction (RCM) cyclization to obtain the target polypeptide. Finally, the target polypeptide is cleaved from the resin for purification. The above solid-phase polypeptide chain synthesis and purification steps were completed by China Peptide Biochemical Co., Ltd. Among them, two S-pentenylalanines (S5) are inserted into the i, i+4 positions in the amino acid sequence of the polypeptide CM4, thereby obtaining modified polypeptides of different sequences (for the amino acid sequence, refer to the sequence table SEQ...

Embodiment 2

[0040] Example 2 Detection of binding ability of polypeptide and TRB3 protein by surface plasmon resonance

[0041] The surface plasmon resonance experiment was carried out in a surface plasmon resonance instrument Biacore T200, and the operation steps were carried out according to the instructions of the plasmon resonance instrument Biacore T200. Specific steps are as follows:

[0042] 1. The purified TRB3 protein (purchased from RD Company) was amino-coupled to a CM5 chip (purchased from GE Company), and the unbound protein was eluted at a flow rate of 10 μL / min, and the surface of the chip was equilibrated for 2 hours. For the specific steps of amino coupling, elution and equilibration, please refer to the relevant instructions of GE's CM5 chip.

[0043] 2. Automatically inject 250 μL of CM4-S01~CM4-S10 and CM4 polypeptide fragments prepared in Example 1 with different concentrations (800, 400, 200, 50, 12.5, 6.25 and 3.125nM), and the entire surface plasmon resonance expe...

Embodiment 3

[0046] Embodiment 3 Circular dichroism method detects the alpha helical rate of polypeptide

[0047] The α-helix rate of the polypeptide was detected with a circular dichroism spectrometer (purchased from Jasco, Japan). Dissolve the polypeptides CM4, CM4-S01, CM4-S02, CM4-S03, CM4-S04, CM4-S05, CM4-S06, CM4-S07, CM4-S08, CM4-S09, CM4-S10 prepared in Example 1 Into the PBS solution, the concentration on the circular dichroism analyzer was adjusted to 1 mg / mL, and the results are shown in Table 2. Table 2 shows that the α-helix rate of polypeptide CM4-S01, CM4-S02, CM4-S03, CM4-S04, CM4-S05, CM4-S06, CM4-S07, CM4-S08, CM4-S09, CM4-S10 is significantly higher in the polypeptide CM4. The maintenance of the α-helical rate of the polypeptide is an important index to increase the stability of the polypeptide. Therefore, the increase of the α-helical rate of the polypeptide CM4-S01-CM4-S10 will enhance its stability. Therefore, the increase of the α-helix rate of the polypeptide CM...

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Abstract

The invention discloses a polypeptide or derivatives thereof for promoting C-Myc protein degradation in a targeted way and application of the polypeptide or derivatives thereof in preparation of medicines for preventing and treating tumors. The polypeptide has an amino acid sequence as shown by substituting two or more amino acids in an amino acid sequence as shown in SEQ ID No.1 in a sequence table with unnatural amino acids with connectable side chains; the derivatives include chimeric peptides formed by linking the polypeptide and cell penetrating peptides, fusion peptides formed by the polypeptide and virus, the methylated polypeptide, the glycosylated polypeptide and the PEGylated polypeptide. The polypeptide or derivatives thereof can specifically bond with TRB3 to block interactionof TRB3 and C-Myc protein and promote degradation of the C-Myc protein, so that the polypeptide or derivatives thereof can be applied to preparation of medicines for preventing and treating tumors. The medicines prepared from the polypeptide or derivatives thereof have the advantages of remarkable curative effect, small toxic and side effect and safe use in tumor disease treatment.

Description

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Claims

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Application Information

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Owner BEIJING WEIFENG YIMIN TECH
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