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A kind of cyclic polypeptide for resisting Candida albicans and its preparation method

A cyclic polypeptide and cyclic technology, applied in the field of antibacterial agents, can solve the problems of life and health hazards of patients, and achieve the effects of improving polypeptide stability, good antibacterial effect and low MIC value

Active Publication Date: 2022-02-11
CHANGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, antibiotics are the main means of treating Candida albicans, but the long-term use of antibiotics in large quantities leads to the stubborn drug resistance of pathogenic bacteria, causing serious harm to the lives and health of patients

Method used

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  • A kind of cyclic polypeptide for resisting Candida albicans and its preparation method
  • A kind of cyclic polypeptide for resisting Candida albicans and its preparation method
  • A kind of cyclic polypeptide for resisting Candida albicans and its preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] The method of the present invention adopts the conventional solid-phase Fmoc method, that is, the monomer amino acid protected by Fmoc on the solid-phase resin is deprotected to expose the amino group, and forms a peptide bond with the carboxyl group of the amino acid in the solution through a condensation reaction, thereby linking the amino acid to the On the resin, the peptide chain is extended from the C-terminus to the N-terminus.

[0025] 1. Basic materials:

[0026] (1) Resin and linking molecule: The resin selected by the solid-phase Fmoc method is Rink Amide- resin. This kind of resin has very good swelling property, which can make the condensation reaction between the peptide chains better, and there is enough network space to meet the growing peptide chains. HBTU and HOBt are used as linking molecules to immobilize the polypeptide molecules on the resin.

[0027] (2) Monomer: The monomer used in the synthesis is a chemically modified α-amino acid.

[0028...

Embodiment 2

[0044] In the fourth step, repeat the second and third steps, add monomer amino acids repeatedly, according to LE 46 RRCR D PPFRCWE 46 The sequence of RRRRRRR sequences is synthesized from right to left until the synthesis is complete.

[0045] Other steps are the same as in Example 1, and the polypeptide sequence AM-66 ( figure 1 ).

[0046] The MIC value of the synthesized cyclic polypeptide is 4.46.

Embodiment 3

[0048] In the fourth step, repeat the second and third steps, add monomer amino acids repeatedly, according to RRE 46 RCR D PPFRCWRE 46 The sequence of RRRRRRR sequences is synthesized from right to left until the synthesis is complete.

[0049] Other steps are the same as in Example 1, and the polypeptide sequence AM-68 ( figure 1 ).

[0050] The MIC value of the synthesized cyclic polypeptide is 4.21.

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Abstract

The invention belongs to the technical field of antibacterial agents, and in particular relates to a cyclic polypeptide for resisting Candida albicans and a preparation method thereof. The amino acid sequence of the cyclic polypeptide is shown in SEQ ID NO.1, which is an intramolecular cyclic polypeptide, and an intramolecular disulfide bond is formed between two cysteine ​​residues in its amino acid sequence to form a molecular Inner loop structure, in which the C-terminal end is composed of 8 arginines, the sequence contains two unnatural amino acids, and the proline at the β-turn angle of the polypeptide is replaced with D PRO‑ L PRO to increase stability in beta-turns. The cyclic polypeptide of the invention has simple amino acid sequence structure and convenient synthesis, is used for the prevention and treatment of diseases caused by Candida albicans, and has high antibacterial activity.

Description

technical field [0001] The invention belongs to the technical field of antibacterial agents, and in particular relates to a cyclic polypeptide for resisting Candida albicans and a preparation method thereof. Background technique [0002] Candida albicans (canidia Albicans) is a fungus that usually exists in the oral cavity, upper respiratory tract, intestinal tract and vagina of normal people. It is generally small in number in normal organisms and does not cause diseases. When the body's immune function or general defense power declines or If the mutual restriction of normal flora is out of balance, the bacteria multiply in large numbers and change their growth form (sprout mycelium phase) to invade cells and cause diseases. [0003] In recent years, with the application of large doses of antibiotics, hormones, immunosuppressants, and the development of organ transplantation, its incidence rate is gradually increasing, and it can endanger life and cause serious consequences...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K14/00A61K38/16A61P31/10
Inventor 王建浩王建鹏邱琳滕一万柳丽王苏南马剑鹤徐以洋杨菲马秀娟罗海燕
Owner CHANGZHOU UNIV
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