A polypeptide targeting the PDZ domain of syntenin protein and its dimer

A dimer and domain technology, applied in the field of peptides targeting the PDZ domain of Syntenin protein and their dimers, can solve the problems of low affinity and high effective concentration of small molecule inhibitors

Active Publication Date: 2021-07-06
SHANGHAI FIRST MATERNITY & INFANT HOSPITAL
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0008] The purpose of the present invention is to provide a high-affinity inhibitor targeting the Syntenin protein, which can inhibit the migration, proliferation and invasion of cancer ce

Method used

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  • A polypeptide targeting the PDZ domain of syntenin protein and its dimer
  • A polypeptide targeting the PDZ domain of syntenin protein and its dimer
  • A polypeptide targeting the PDZ domain of syntenin protein and its dimer

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Embodiment Construction

[0044] The present invention will be further described below in conjunction with specific examples.

[0045] 1. Peptide synthesis and affinity characterization

[0046] Select the following four polypeptide sequences from the literature: RVAFFEEL (polypeptide epitope of Merlin protein), TNEFYA (polypeptide epitope of syndecan protein), DKEYYV (polypeptide epitope of neurexin protein), LEDSVF (polypeptide epitope of interleukin-5 receptorα protein) .

[0047] In order to facilitate subsequent characterization, a FAM fluorescent group was added to the N-terminus, and GS amino acid was used as the spacer between the fluorescent group and the functional amino acid region.

[0048] 1. Synthesis of monomeric polypeptide

[0049] 1) Using Fmoc chemical solid-phase peptide synthesis, using Fmoc-wang resin, using 5-fold excess of Fmoc-protected amino acids and condensation reagents (HBTU / HOBt) to synthesize peptides.

[0050] 2) Cysteine ​​C is added near the N-terminus of the polyp...

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Abstract

The invention discloses a polypeptide targeting Syntenin protein and its dimer and application, belonging to the technical field of biomedicine. The amino acid sequence of the polypeptide is Cys-Asp-Lys-Glu-Tyr-Φ-Val or Cys-Asp-Lys-Glu-Φ-Trp-Val, wherein Φ is 3-(2-naphthyl)-L-propane acid. The polypeptide provided by the invention is obtained by optimizing the amino acid of the screened natural polypeptide ligand, which significantly improves its affinity with the tandem PDZ domain of the Syntenin protein. The dimeric polypeptide obtained by dimerizing the above polypeptides greatly improves the affinity with the tandem PDZ domain, and can effectively inhibit the migration, proliferation, and invasion of various cancer cells with high expression of Syntenin at a concentration of 10uM, and at the same time does not Produce other toxic and side effects, and provide design ideas for the development of drugs for the treatment of metastasis and invasion of malignant tumors with high expression of Syntenin.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a polypeptide targeting the PDZ domain of Syntenin protein, its dimer and its application. Background technique [0002] Syntenin is a class of intracellular adapter proteins widely present in prokaryotes and eukaryotes. Studies have found that Syntenin protein is highly expressed in a variety of highly invasive malignant tumors, and its expression is up-regulated with the progression of tumor metastasis. [0003] Syntenin consists of N-terminal domain (N-terminal domain, NTD), two tandem PDZ domains (postsynaptic density protein, disc large and zonula occludens, PDZ) and C-terminal domain (C-terminal domain, CTD). The PDZ domain of syntenin protein can specifically bind to the PDZ binding motif (PBM) at the C-terminus of different membrane receptors, and the diversity of PDZ domain-binding receptors leads to the diversity of syntenin functions. [0004] During the developm...

Claims

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Application Information

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IPC IPC(8): C07K7/06C07K19/00A61K38/08A61K47/64A61P35/00
CPCA61K38/00A61P35/00C07K7/06C07K2319/10
Inventor 于永生刘佳慧夏江冯茜金莉萍王凯周倩
Owner SHANGHAI FIRST MATERNITY & INFANT HOSPITAL
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