Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Polypeptide for selectively degrading PD-L1 protein on tumor cell membrane and application

A PD-L1, cell membrane technology, used in antitumor drugs, peptide/protein components, medical preparations containing active ingredients, etc.

Active Publication Date: 2021-07-06
NANKAI UNIV
View PDF1 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there is no research on the use of small molecules to control the expression level of PD-L1 on the tumor cell membrane, and it is used in the preparation of tumor immune drugs

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Polypeptide for selectively degrading PD-L1 protein on tumor cell membrane and application
  • Polypeptide for selectively degrading PD-L1 protein on tumor cell membrane and application
  • Polypeptide for selectively degrading PD-L1 protein on tumor cell membrane and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0072] Example 1 Polypeptide Ada-GG D f D f D wxya D N D Y D S D K D P D T D D. D R D Q D Y D h D Synthesis of F

[0073] It was synthesized by Fmoc-short peptide solid-phase synthesis method. The specific steps are:

[0074] 1) Weigh 0.5mmol 2-Cl-Trt resin in a solid phase synthesizer, add 10mL of anhydrous dichloromethane (DCM), place on a shaker and shake for 10min to fully swell the 2-Cl-Trt resin;

[0075] 2) Remove the DCM from the solid-phase synthesizer equipped with 2-Cl-Trt resin with ear washing ball;

[0076] 3) Dissolve 0.5 mmol of Fmoc-protected amino acid (Fmoc-D-Phe-OH) in 10 mL of anhydrous DCM, add 1 mmol of DIEPA, then transfer to the above-mentioned solid-phase synthesizer, and react at room temperature for 1 h;

[0077] 4) Sealing: Remove the reaction solution in the solid-phase synthesizer with ear wash balls, then wash with 10 mL of anhydrous DCM for 1 min each time, and wash 5 times in total. Add the prepared volume ratio of anhydrous D...

Embodiment 2

[0083] Example 2 Polypeptide Ada-GGGG D wxya D N D Y D S D K D P D T D D. D R D Q D Y D h D Synthesis of F

[0084] A polypeptide without phenylalanine was synthesized according to the Fmoc-short peptide solid-phase synthesis method in Example 1. The obtained polypeptide is referred to as OF, and its amino acid sequence is shown in SEQ ID NO.2. Detect the polypeptide obtained in this embodiment 2 by high performance liquid chromatography mass spectrometry, the results are shown in figure 2 , structural formula as shown in claim 3.

Embodiment 3

[0085] Example 3 Polypeptide Ada-GGG D f D wxya D N D Y D S D K D P D T D D. D R D Q D Y D h D Synthesis of F

[0086] A polypeptide containing 1 phenylalanine was synthesized according to the Fmoc-short peptide solid-phase synthesis method in Example 1. The obtained polypeptide is referred to as 1F, and its amino acid sequence is shown in SEQ ID NO.3. Detect the polypeptide obtained in this embodiment 3 by high performance liquid chromatography mass spectrometry, the results are shown in image 3 , structural formula as shown in claim 4.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention relates to the technical field of medicine and pharmacy, in particular to polypeptide for selectively degrading PD-L1 protein on a tumor cell membrane and application. The polypeptide can be subjected to enzymatic in-situ self-assembly under the action of ALP overexpressed outside a tumor cell, and a DPPA-1 sequence capable of being specifically combined with PD-L1 exists in a polypeptide molecule, so that the self-assembled polypeptide nanofiber can be selectively combined with the PD-L1 on the tumor cell membrane to simulate a partial denaturation state of the PD-L1; and the PD-L1 protein is degraded through a proteasome way after being swallowed into cells, so that the PD-L1 protein on the tumor cell membrane is effectively degraded, the control of tumor cells on an immune system is relieved, and a new thought is provided for the preparation of tumor immunotherapy drugs.

Description

technical field [0001] The invention relates to the field of medicine and pharmaceutical technology, in particular to a polypeptide that selectively degrades PD-L1 protein on tumor cell membranes and its application. Background technique [0002] Immunotherapy has become the fourth tumor treatment after surgery, radiotherapy and chemotherapy, especially the treatment targeting immune checkpoint molecules has achieved very positive therapeutic effects in the clinical treatment of tumors. In many studies related to immunotherapy, the T-cell-based PD-1 (programmed cell death receptor 1) / PD-L1 (programmed cell death ligand 1) immune checkpoint pathway is considered to be the key to extending immune response. A pillar of therapy that has gained enormous attention. Previous studies have shown that overexpression of PD-L1 in tumor cells can enhance tumor viability and metastasis, leading to tumor immune escape. Tumor cells will carry out immunosuppression through the PD-1 / PD-L1 p...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07K7/08A61K38/10A61P37/04A61P35/00
CPCC07K7/08A61P35/00A61P37/04A61K38/00
Inventor 杨志谋王玲王宇涵
Owner NANKAI UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com