Peptides and their applications

Abstract

The invention discloses a polypeptide and application thereof. The polypeptide contains a sequence represented by formula (I) or salt: P<1>-Ala-Gly-X1-Ala-X2-X3-X4-P<2>. By inhibiting the interaction of proteins APC / Asef in a cancer cell, an anti-tumor effect is achieved. The anti-tumor polypeptide has wide spectrum property and is capable of inhibiting and killing multiple cancer cells, short in peptide chain length, high in anti-tumor activity, stable and unlikely to be inactivated.

Description

technical field

[0001] The invention belongs to the field of polypeptides, and more specifically relates to an anti-tumor polypeptide and its application. Background technique

[0002] The interaction between specific intracellular proteins constitutes a variety of intracellular signal transduction pathways, which are crucial to the survival of normal cells and cancer cells, and are an important source of drug targets. Studies have found that there is a specific protein-protein interaction in cancer cells—the truncated APC (Adenomatous Polyposis Coli) / Asef (APC-stimulated guanine nucleotide exchange factor) protein interaction, which It plays an important role in the occurrence and development of tumors and can become a new drug target for cancer treatment.

[0003] APC is involved in regulating processes such as cell adhesion and cell migration under physiological conditions. Clinical studies have confirmed that in patients with colon cancer, breast cancer, and lung cance...

Examples

Embodiment 1

[0046] Example 1 Solid phase synthesis, cleavage, purification and identification of polypeptide 1

[0047] 1.1 Solid phase synthesis of polypeptide 1

[0048] The present invention utilizes a polypeptide synthesizer to synthesize polypeptide 1 (Ac-AGEALYE-NH2) by solid-phase synthesis: using DMF as a solvent, the concentration of various α-amino acids protected by Fmoc is 0.25M, the concentration of HBTU solution and HOBt solution is 0.33M, the concentration of piperidine solution is 200ml / L, and the concentration of DIEA solution is 174.2ml / L.

[0049] 1.1.1 Fmoc protecting group

[0050] Take 1g of Rink Amide MBHA Resin (the degree of substitution of the resin is 0.40mmol / g, and the resin is protected by Fmoc) into the peptide bottle, add an appropriate amount of CH 2 Cl 2 Swell the resin, then put the CH 2 Cl 2 Take out and add 6ml 20% piperidine / DMF solution, shake for 5 minutes, drain, then add 6ml 20% piperidine / DMF solution, shake for 15 minutes, then drain, wash ...

Embodiment 2

[0059] Example 2 Prepare 5 mg of polypeptide 2Ac-AGEAIYE-NH2 according to the same method as in Example 1, ESI: 791.8 [M-H] - , HPLC: 98.3%.

Embodiment 3

[0060] Example 3 Prepare polypeptide 3Ac-AGESLYE-NH2 Ac-AGEAIYE-NH2 5 mg according to the same method as Example 1, ESI: 807.9 [M-H] - , HPLC: 98.1%.

technical field

[0001] The invention belongs to the field of polypeptides, and more specifically relates to an anti-tumor polypeptide and its application. Background technique

[0002] The interaction between specific intracellular proteins constitutes a variety of intracellular signal transduction pathways, which are crucial to the survival of normal cells and cancer cells, and are an important source of drug targets. Studies have found that there is a specific protein-protein interaction in cancer cells—the truncated APC (Adenomatous Polyposis Coli) / Asef (APC-stimulated guanine nucleotide exchange factor) protein interaction, which It plays an important role in the occurrence and development of tumors and can become a new drug target for cancer treatment.

[0003] APC is involved in regulating processes such as cell adhesion and cell migration under physiological conditions. Clinical studies have confirmed that in patients with colon cancer, breast cancer, and lung cance...

Examples

Embodiment 1

[0046] Example 1 Solid phase synthesis, cleavage, purification and identification of polypeptide 1

[0047] 1.1 Solid phase synthesis of polypeptide 1

[0048] The present invention utilizes a polypeptide synthesizer to synthesize polypeptide 1 (Ac-AGEALYE-NH2) by solid-phase synthesis: using DMF as a solvent, the concentration of various α-amino acids protected by Fmoc is 0.25M, the concentration of HBTU solution and HOBt solution is 0.33M, the concentration of piperidine solution is 200ml / L, and the concentration of DIEA solution is 174.2ml / L.

[0049] 1.1.1 Fmoc protecting group

[0050] Take 1g of Rink Amide MBHA Resin (the degree of substitution of the resin is 0.40mmol / g, and the resin is protected by Fmoc) into the peptide bottle, add an appropriate amount of CH 2 Cl 2 Swell the resin, then put the CH 2 Cl 2 Take out and add 6ml 20% piperidine / DMF solution, shake for 5 minutes, drain, then add 6ml 20% piperidine / DMF solution, shake for 15 minutes, then drain, wash ...

Embodiment 2

[0059] Example 2 Prepare 5 mg of polypeptide 2Ac-AGEAIYE-NH2 according to the same method as in Example 1, ESI: 791.8 [M-H] - , HPLC: 98.3%.

Embodiment 3

[0060] Example 3 Prepare polypeptide 3Ac-AGESLYE-NH2 Ac-AGEAIYE-NH2 5 mg according to the same method as Example 1, ESI: 807.9 [M-H] - , HPLC: 98.1%.

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