A polypeptide that selectively degrades pd-l1 protein on tumor cell membrane and its application

A selective and biologically active technology, applied in the field of peptides and applications that selectively degrade PD-L1 protein on tumor cell membranes, to achieve high biocompatibility, inhibit growth speed, and restore immune killing effects

Active Publication Date: 2022-08-05
NANKAI UNIV
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  • 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

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  • A polypeptide that selectively degrades pd-l1 protein on tumor cell membrane and its application
  • A polypeptide that selectively degrades pd-l1 protein on tumor cell membrane and its application
  • A polypeptide that selectively degrades pd-l1 protein on tumor cell membrane and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0072] Example 1 Polypeptide Ada-GG D F D F D pYG 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 0.5 mmol of 2-Cl-Trt resin in a solid phase synthesizer, add 10 mL of anhydrous dichloromethane (DCM), place it on a shaking table and shake for 10 min to fully swell the 2-Cl-Trt resin;

[0075] 2) Use ear washing balls to remove DCM from the solid-phase synthesizer equipped with 2-Cl-Trt resin;

[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 solid-phase synthesizer, and react at room temperature for 1 h;

[0077] 4) Closure: remove the reaction solution in the solid-phase synthesizer with ear washing balls, then wash with 10 mL of anhydrous DCM for 1 min each, for a total of 5 washes, add the prepared volume ratio of anhydrous DC...

Embodiment 2

[0083] Example 2 Polypeptide Ada-GGGG D pYG 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] Polypeptides without phenylalanine were synthesized according to the solid-phase synthesis method of Fmoc-short peptide in Example 1. The obtained polypeptide is referred to as OF, and its amino acid sequence is shown in SEQ ID NO.2. The polypeptide obtained in Example 2 was detected by high-performance liquid chromatography-mass spectrometry, and the results were shown in figure 2 , the structural formula is shown in claim 3.

Embodiment 3

[0085] Example 3 Polypeptide Ada-GGG D F D pYG 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 one phenylalanine was synthesized according to the solid-phase synthesis method of Fmoc-short peptide in Example 1. The obtained polypeptide is referred to as 1F for short, and the amino acid sequence is shown in SEQ ID NO.3. The polypeptide obtained in Example 3 was detected by high-performance liquid chromatography-mass spectrometry, and the results were shown in image 3 , the structural formula is shown in claim 4.

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Abstract

The invention relates to the technical field of medicine and pharmacy, in particular to a polypeptide for selectively degrading PD-L1 protein on tumor cell membranes and its application. The polypeptide of the present invention can undergo enzymatic in situ self-assembly under the action of ALP overexpressed in tumor cells, and the polypeptide molecule has a molecule that can specifically bind to PD-L1. D The PPA-1 sequence enables the self-assembled polypeptide nanofibers to selectively bind to PD-L1 on the tumor cell membrane to simulate its partial denaturation state, and is then endocytosed into cells and degraded through the proteasome pathway, thereby effectively degrading The PD-L1 protein on the tumor cell membrane relieves the control of tumor cells on the immune system and provides new ideas for the preparation of tumor immunotherapy drugs.

Description

technical field [0001] The invention relates to the technical field of medicine and pharmacy, in particular to a polypeptide for selectively degrading PD-L1 protein on tumor cell membranes and its application. Background technique [0002] Immunotherapy has become the fourth tumor treatment method after surgery, radiotherapy and chemotherapy. In particular, the treatment of immune checkpoint molecules has achieved very positive therapeutic effects in the clinical treatment of tumors. Among numerous immunotherapy-related studies, the T cell-based PD-1 (programmed death receptor 1) / PD-L1 (programmed death ligand 1) immune checkpoint pathway is considered to expand immunity The mainstay of therapy has gained enormous attention. Previous studies have shown that overexpression of PD-L1 in tumor cells enhances tumor viability and metastasis, leading to tumor immune escape. Tumor cells will undergo immunosuppression through the PD-1 / PD-L1 pathway to achieve local growth and compl...

Claims

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Application Information

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Patent Type & Authority Patents(China)
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
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