Tumor-targeted polypeptide, polypeptide coupling medicine and application of tumor-targeted polypeptide and polypeptide coupling medicine

A tumor-targeting, peptide-coupling technology, applied in the direction of anti-tumor drugs, drug combinations, peptides, etc., can solve the problems of drug dosage limitation, large damage to normal cells, patient drug resistance, and unsatisfactory treatment effects, etc., to achieve Increase the therapeutic effect and avoid the effect of premature degradation

Active Publication Date: 2022-04-22
深圳深创生物药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, because no targeted therapy has been achieved, the damage to normal cells is relatively large, so the dosage of the drug is greatly limited, and the patient's drug resistance and therapeutic effect are not very ideal.

Method used

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  • Tumor-targeted polypeptide, polypeptide coupling medicine and application of tumor-targeted polypeptide and polypeptide coupling medicine
  • Tumor-targeted polypeptide, polypeptide coupling medicine and application of tumor-targeted polypeptide and polypeptide coupling medicine
  • Tumor-targeted polypeptide, polypeptide coupling medicine and application of tumor-targeted polypeptide and polypeptide coupling medicine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Example 1: Synthesis of polypeptide sequences (X is none)

[0046] The peptide sequence was synthesized by Fmoc solid-phase peptide synthesis technology. Weigh 20 grams of Wang resin with a substitution degree of 1.0 mmol / g in a solid-phase reaction column, add DMF, and swell with nitrogen gas bubbles for 60 minutes; weigh 6.67 grams (10 mmol) of Fmoc-Asp-ODmab, and 1.6 grams (12 mmol) of HOBt , DMAP 0.12g (1mmol), dissolved in DMF, added 2.3mL DIC (15mmol) in ice-water bath at 0°C, activated for 5 minutes, added to the reaction column, reacted for 1.5 hours, added 14mL acetic anhydride and 12mL pyridine, mixed and blocked for 24 hours , washed three times with DCM, dried the resin after shrinking with methanol, and obtained 26 grams of Fmoc-Asp-ODmab-WangResin in total, and the detection degree of substitution was 0.25 mmol / g.

[0047] Then weigh a total of 16 grams (4 mmol) of the above-mentioned Fmoc-Asp-ODmab-Wang Resin, according to the conventional method of Fmoc...

Embodiment 2

[0051] Embodiment 2: the synthesis of polypeptide sequence (X is Cys)

[0052] Peptide resin was obtained by Example 1, weighed 10.4g (two-thirds, 2mmol) into the solid-phase reaction column, added DMF to swell for 30 minutes, and then continued to couple Boc-Cys according to the standard method of Fmoc solid-phase peptide synthesis (StBu)-OH, after the coupling is completed, add a DMF solution containing 10mmol (5eq) tributylphosphine, react for 1 hour, selectively remove the StBu protecting group of the side chain of the Cys residue, wash with DMF for 5 times, Wash with methanol for 10 minutes and dry in vacuum for 4 hours to obtain Boc-Cys-Arg(Pbf)-Arg(Pbf)-Arg(Pbf)-Arg(Pbf)-Arg(Pbf)-Arg(Pbf) with exposed Cys side chain mercapto groups. )-Arg(Pbf)-Arg(Pbf)-D-Glu(OtBu)-PEG 4 -Cyclo(Lys-Arg(Pbf)-Gly-Asp-D-Phe)-Wang Resin (where: D-Phe-main chain carboxyl group and Lys main chain amino group form an amide ring; PEG 4 A total of 10.8 g of peptide resins linked to the amino gr...

Embodiment 3

[0053] Embodiment 3: the coupling of paclitaxel (PTX) and polypeptide

[0054] Take by weighing the peptide resin 5.2g (1mmol) that embodiment 1 obtains, add the solid-phase reaction column that has jacket, after DMF swells resin 30 minutes, according to the standard method of Fmoc solid-phase peptide synthesis, continue to couple Fmoc on resin -GABA-OH (Fmoc-γ-aminobutyric acid), remove the Fmoc protecting group, then add DMF solvent, add 5mmol (5eq) of 4-nitrophenyl chloroformate (chloroformic acid-4-nitrophenyl ester), add 2ml pyridine, the reaction temperature was heated to 60°C through a jacket, and the phase reaction was carried out for 6 hours, and the resin was washed 5 times with DMF.

[0055] Add 12mmol of HOBt (12eq), 1mol of DMAP (1eq), 15mmol of DIC (15eq) and 10mmol of paclitaxel (10eq) to the above-mentioned washed peptide resin, add DCM as a reaction solvent, and react at room temperature for 4 hours to obtain paclitaxel Peptide resin coupled to the polypeptid...

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PUM

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Abstract

The invention discloses a tumor targeting polypeptide, a polypeptide coupling drug and application of the tumor targeting polypeptide and the polypeptide coupling drug. The polypeptide sequence of the tumor targeting polypeptide is X-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-D-Gl-PEG4-Cyclo (Lys-Arg-Gly-Asp-D-Phe), the carboxyl group of the main chain of D-Phe and the amino group of the main chain of Lys form an amide ring, and PEG4 is connected with the amino group of the side chain of Lys; in the formula, X represents that the amino acid residue is Cys or does not exist. The tumor targeting polypeptide provided by the invention has targeting property and penetrability, and when the tumor targeting polypeptide is used as a carrier of a small-molecule anti-tumor drug to prepare a polypeptide coupling drug, the anti-tumor drug can directionally penetrate through cell membranes of cancer cells, release of the small-molecule drug is completed, and specific targeting therapy of tumors is carried out.

Description

technical field [0001] The invention relates to the field of products involved in the treatment of cancer, especially the treatment of pancreatic cancer and triple-negative breast cancer, and specifically relates to a tumor-targeting polypeptide, a polypeptide-coupled drug and applications thereof. Background technique [0002] In early 2021, the International Agency for Research on Cancer (IARC) of the World Health Organization released the latest global cancer burden data for 2020. In 2020, there will be 10.07 million new cancer cases in men worldwide, and 9.23 million new cancer cases in women. According to the data, the number of new cancers and cancer deaths in China ranks first in the world. [0003] At present, the treatment methods for cancer mainly include surgery, chemotherapy, and radiotherapy, among which chemotherapy is one of the main methods for treating cancer. However, during the course of treatment, the patient has obvious side effects such as nausea, vom...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K1/04C07K7/50A61K47/64A61K31/7068A61K31/704A61K31/337A61P35/00
CPCC07K1/04C07K7/50A61K47/64A61K31/7068A61K31/704A61K31/337A61P35/00
Inventor 戴政清张凌云王宇恩马亚平
Owner 深圳深创生物药业有限公司
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