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New Delhi metallo-beta-lactamase inhibitory peptide and application thereof

A technology of lactams, phe-cys-d-phe, applied in the treatment of drug-resistant bacterial infections, tripeptide inhibitors of metallo-β-lactamases, preparation of antibacterial drugs and prevention, can solve difficult problems in clinical treatment , to achieve the effect of easy control of product quality, simple structure and simple method

Inactive Publication Date: 2014-02-19
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Evolving mutant strains make clinical treatment more difficult, so the development of broad-spectrum MBLs inhibitors has become a major challenge in the medical field

Method used

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  • New Delhi metallo-beta-lactamase inhibitory peptide and application thereof
  • New Delhi metallo-beta-lactamase inhibitory peptide and application thereof
  • New Delhi metallo-beta-lactamase inhibitory peptide and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0066] Preparation of Phe-Cys-D-Phe

[0067] 1. Weigh 2.0g of MBHA (4-toluene hydrogen amine) resin into a clean and dry reaction tube, add an appropriate amount of DMF (dimethylformamide), activate for about 30 minutes, and then weigh Fmoc (fluorenylmethyloxycarbonyl) protection Add 1mmol of Phe, 150mg of DMAP (4-dimethylaminopyridine), add 1ml of 98% DIC (N,N′-diisopropylcarbodiimide) to the reaction tube, and react with DMF as the solvent for 3h. After the reaction is completed, wash with DMF for 4 to 6 times, add appropriate amount of pyridine and acetic anhydride, the volume ratio is 1:1, and react for 30 minutes. After the reaction, wash with DMF 4 to 6 times. Then use 20% piperidine solution to remove the Fmoc of amino acid, remove twice for a total of 15min, 10min+5min. Then wash 4 times with DMF, wash 2 times with methanol, take out a small amount of resin and detect it with ninhydrin detection reagent, the detection is blue, and the next step reaction can be carrie...

Embodiment 2

[0072] Preparation of Antibacterial Pharmaceutical Composition Containing Phe-Cys-D-Phe Inhibitor Peptide (Capsule)

[0073]

[0074] According to the amount of 100 capsules, weigh the above auxiliary materials, grind and sieve them, and mix them evenly, then add cefuroxime sodium and Phe-Cys-D-Phe by equal addition method, fully grind to make them disperse evenly, and then Pass through a 80-mesh sieve, and then fill into capsules.

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Abstract

The invention belongs to the field of biological medicament, and specifically relates to a NDM-1 type metallo-beta-lactamase tripeptide inhibitor with an amino acid sequence of Phe-Cys-D-Phe. Pharmacodynamical experiments prove that the peptide provided by the invention is applicable to preparation of antibacterial medicaments for preventing and treating drug-resistance bacterial infection.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to a tripeptide inhibitor of metallo-beta-lactamase, and in particular to the use of the peptide in the preparation of antibacterial drugs and the prevention and treatment of drug-resistant bacterial infections. Background technique [0002] The production of β-lactamase is one of the important mechanisms leading to drug resistance of bacteria, especially Gram-negative bacteria. They can hydrolyze the β-lactam ring of β-lactam antibiotics, leading to the inactivation of antibiotics. β-lactamases can be divided into serine β-lactamases and metallo-β-lactamases (MBLs). According to the amino acid sequence homology and dependence on metal Zn ions, MBLs are further divided into B1, B2 and B3 subclasses. So far, 18 homologous families have been found in class B1, 3 homologous families in class B2, and 9 homologous families in class B3. Since metallo-β-lactamases can hydrolyze almost all β-la...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K5/087A61K38/06A61P31/04A61K31/546
Inventor 陈姣郑珩劳兴珍
Owner CHINA PHARM UNIV
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