A modified polypeptide based on marine cyclic peptide samoamide A, synthesis method and application

A technology of marine cyclic peptides and synthetic methods, applied in the biological field, can solve problems such as poor anti-tumor activity, achieve excellent anti-tumor activity, reduce steric hindrance, and improve cyclization efficiency

Active Publication Date: 2022-02-25
ANHUI POLYTECHNIC UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0008] Aiming at the defect of poor antitumor activity of a cyclic peptide Samoamide A naturally extracted from marine algae, the present invention provides a method that uses two 4-Br-Phes to replace two phenylalanines in the original Samoamide A cyclic peptide Acid, obtain the transformation polypeptide SamoamideB based on Samoamide A, described SamoamideB shows more excellent anti-tumor activity relative to Samoamide A

Method used

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  • A modified polypeptide based on marine cyclic peptide samoamide A, synthesis method and application
  • A modified polypeptide based on marine cyclic peptide samoamide A, synthesis method and application
  • A modified polypeptide based on marine cyclic peptide samoamide A, synthesis method and application

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Embodiment 1

[0059] The synthesis of the tumor suppressor active peptide B in this embodiment specifically includes the following steps:

[0060] (1) Coupling reaction between resin and amino acid

[0061] Weigh 2.00 g of 2-chlorotrityl chloride resin and put it into the sand core tube for polypeptide synthesis. Add DMF and use a rotary vane vacuum pump to blow and wash for 5-10 seconds, then use a circulating water-type multi-purpose vacuum pump to filter the liquid, add DCM to soak the resin and blow for 2-3 minutes to fully expand and then filter. Weigh 451.4 mg of Fmoc-Val-OH and put it into a sand core tube, add DCM as a reaction solvent, add 1 mL of DIEA dropwise as a condensation reagent, blow the reaction at room temperature for 30 minutes, pump out the liquid, add DMF to wash 4 times and filter with suction. Add DCM again, add dropwise 4mL of anhydrous methanol and 4mL DIEA to react for 30min, and cap the unreacted sites of the resin. After the reaction was finished, filter with...

Embodiment 2

[0082] This embodiment is an anti-tumor activity verification experiment for Samoamide A and Samoamide B, including the following steps:

[0083] (1) DPP-4 enzyme activity inhibition experiment

[0084] The imported DPP-4 enzyme inhibitor sitagliptin and the experimental method provided were used to verify the inhibitory effect of several derivatives on DPP-4 enzyme activity. Take an opaque 96-well black microtiter plate, and add 1 μL DPP-4 enzyme solution and 49 μL test buffer dropwise to each control.

[0085] Then set up each group of experiments:

[0086] Group 1-blank group: without adding any substance;

[0087] Group 2-sample group to be tested: Add 25 μL of peptide solution with DMSO as solvent, the concentration is 100 μg / mL, and test the experimental groups of the peptide solutions of Samoamide A and Samoamide B respectively;

[0088] Group 3-inhibitor comparison group: pipette 2 μL of the sitagliptin inhibitor mother solution provided in the kit, add buffer to di...

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Abstract

The invention belongs to the field of biotechnology, and discloses a modified polypeptide based on the marine cyclic peptide Samoamide A, a synthesis method and an application. The structure of the active peptide is: cyclic-(Leu-Pro-Pro-(4-Br-Phe) ‑Ile‑Pro‑(4‑Br‑Phe)‑Val). The synthesis method comprises the following steps: 1) using a resin to perform a coupling reaction with an amino acid, so that a linear peptide is coupled to the resin; 2) adding a cutting solution to the resin for reaction, collecting the solution after the reaction, and adding DIEA dropwise to the solution Adjust the pH value to be neutral to obtain a crude product solution of the linear peptide; 3) add the crude product solution of the linear peptide dropwise into the cyclic peptide reaction system to synthesize the cyclic peptide. The present invention replaces the two phenylalanines in the original Samoamide A cyclic peptide by two Br-phenylalanines, and obtains the derivative SamoamideB based on Samoamide A through a suitable solid-phase synthesis method, and the prepared SamoamideB is aimed at DPP ‑4 Enzyme activity inhibition rate and tumor cytotoxicity have been significantly improved, reflecting more excellent anti-tumor activity.

Description

technical field [0001] The invention belongs to the field of biotechnology, and in particular relates to a modified polypeptide based on the marine cyclic peptide Samoamide A, a synthesis method and an application. Background technique [0002] Peptide compounds have become an important research direction of anti-tumor chemical drugs due to their advantages of low toxicity, clear target specificity and small molecular weight. In particular, cyclic peptide compounds have attracted more and more attention from researchers because of their long half-life in vivo, relatively stable structure, and strong cell membrane penetration. [0003] Samoamide A[-(Leu-Pro-Pro-Phe-Ile-Pro-Phe-Val)-] is a cyclic peptide naturally extracted from marine algae, and has a good toxic effect on tumor cells. However, the natural extraction of Samoamide A has low extraction yield and poor activity, and cannot be produced and applied on a large scale. Therefore, it is necessary to invent a method for...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K7/64C07K1/06C07K1/04A61K38/12A61P35/00
CPCC07K7/64A61P35/00A61K38/00
Inventor 葛飞陈刘旺李婉珍陶玉贵宋平朱龙宝张伟伟
Owner ANHUI POLYTECHNIC UNIV
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