A kind of solid-phase synthesis method and application of CO releasing molecule based on polypeptide-manganese-carbonyl complex

A solid-phase synthesis and complex technology, which is applied in the preparation method of peptides, chemical instruments and methods, peptides, etc., can solve the problems of lengthy and time-consuming synthesis process, complex and time-consuming preparation of SAAC, and shorten the synthesis time and cost , The effect of saving liquid phase purification steps

Active Publication Date: 2021-11-19
SOUTH CHINA UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the preparation of SAAC in the existing peptide-metal complex synthesis scheme is relatively complicated and time-consuming (it needs to be purified by liquid phase organic reaction and column chromatography)
Moreover, if you want to adjust the wavelength of the light source by changing the type of nitrogen atom heterocyclic compound or adding substituent groups on the heterocyclic ring, you need to re-synthesize a new SAAC and then carry out step-by-step peptide synthesis, making the complete synthesis process more tedious time consuming

Method used

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  • A kind of solid-phase synthesis method and application of CO releasing molecule based on polypeptide-manganese-carbonyl complex
  • A kind of solid-phase synthesis method and application of CO releasing molecule based on polypeptide-manganese-carbonyl complex
  • A kind of solid-phase synthesis method and application of CO releasing molecule based on polypeptide-manganese-carbonyl complex

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0082] Example 1: The side chain coordinating group is the preparation method of bis-methylenepyridine (dpa) TAT-manganese carbonyl complex:

[0083](1) Preparation of Fmoc-Arg(Pbf)-MBHA resin: Take 500mg Rink Amide MBHA resin in a peptide synthesis tube with a loading capacity of 0.2-0.8mmol / g, add 15mL DMF to swell twice at room temperature, 15min each time, Drain, add 10mL 20% piperidine / DMF to the resin, shake at room temperature for 5min, wash twice with DMF, add 10mL 20%piperidine / DMF again, shake for 5min at room temperature, wash with DMF, DCM, DMF was washed twice each, and the solvent was drained to obtain the resin that the amino group removed Fmoc protection. Weighed Fmoc-Arg(Pbf)-OH(1mmol), TBTU(2mmol) and DIEA(0.98mmol), and Fmoc-Arg(Pbf )-OH and TBTU were dissolved with a small amount of DMF, added DIEA, and the carboxyl group was activated by shaking at room temperature for 2 minutes. After that, the activated amino acid was added to the resin, shaken and react...

Embodiment 2

[0090] Embodiment 2: The side chain coordination group is the preparation method of double methylene quinoline (dqa) TAT-manganese carbonyl complex:

[0091] (1) According to the method of Example 1, 500 mg of Fmoc-Arg(Pbf)-MBHA resin with a loading capacity of about 0.44 mmol / g was obtained.

[0092] (2) Preparation of TATK7K(Alloc)-MBHA resin: add 15mL DMF to the obtained Fmoc-Arg(Pbf)-MBHA resin and swell twice at room temperature, 15min each time, drain, and then add 10mL 20% ethyl alcohol to the resin Acid anhydride / DMF, react with shaking at room temperature for 20min to block the amino group of the resin that is not coupled with amino acid, prevent its next reaction, wash twice with DMF, DCM, DMF in turn, add 10mL 20% piperidine / DMF to the resin, room temperature Shake the reaction for 5 minutes, wash twice with DMF, add 10 mL of 20% piperidine / DMF again, shake and react at room temperature for 5 minutes, wash twice with DMF, DCM, and DMF in turn, and drain the solvent ...

Embodiment 3

[0098] Example 3: Light-controlled CO release experiment

[0099] Experimental materials: myoglobin (Mb) (sigma aldrich), sodium dithionite, TATK7K (dpa-Mn(CO) 3 ), TATK7K (dqa-Mn(CO) 3 ), PBS buffer, visible violet flashlight (380-415nm, LED, 5W).

[0100] Experimental steps:

[0101] ① The PBS buffer was deoxygenated by bubbling nitrogen gas for 30 minutes.

[0102] ②Use deoxygenated PBS to prepare Mb to a final concentration of 40 μmol / L, and add to a quartz cuvette. Sodium dithionite (final concentration: 3.2mmol / L) was added to reduce Mb.

[0103] ③Add TAT-Mn(CO) 3 Polypeptide-manganese complex (final concentration: 10 μmol / L).

[0104]④Use the visible light purple light flashlight contrast color dish to illuminate, and use the ultraviolet-visible spectrum to record the spectrum of different cumulative illumination time. The result is as Figure 5 , Image 6 shown.

[0105] The following conclusions can be obtained from the changes of the characteristic peaks of...

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Abstract

The invention provides a solid-phase synthesis method and application of a CO releasing molecule based on a polypeptide-manganese-carbonyl complex. This method adopts the Fmoc solid-phase peptide synthesis method, uses side chain Alloc-protected lysine at the site where the side chain modification needs to be introduced, and sequentially condenses Fmoc-protected amino acids from the C-terminal to the N-terminal to obtain a polypeptide with an Alloc-protected side chain Amino resin; remove the Alloc group on the resin to expose free amino groups that can be used for modification reactions; use reductive amination reaction on the resin to modify the free amino groups on the polypeptide chain on the resin into ligands that can be chemically coordinated group; adding manganese pentacarbonyl bromide for chemical coordination on the resin; finally, the target polypeptide is cleaved from the resin and purified to obtain a polypeptide with manganese-carbonyl coordination. The invention helps to study the physiological and biochemical effects of carbon monoxide on specific parts, and at the same time lays a good foundation for the treatment of carbon monoxide in related diseases.

Description

technical field [0001] The invention relates to the technical field of synthesis and preparation of polypeptide-metal complexes, in particular to a solid-phase synthesis method of CO releasing molecules based on polypeptide-manganese-carbonyl complexes and its application. Background technique [0002] Carbon monoxide (CO) has long been considered a toxic gas because of its strong binding to hemoglobin in the body. But at the same time, as an important gas molecule, CO plays a variety of physiological functions such as signal transduction and cell protection in mammals (R. Motterlini, Nat. Rev. Drug. Discov., 2010, 9, 728–743. ). In order to further explore the important role of CO in the life system and its application in clinical medicine, one of the key issues that needs to be solved first is how to realize the safe and controllable fixed-point transportation of CO. [0003] The use of carbon monoxide releasing molecules (CORMs) is one of the feasible options for the co...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K1/04C07K1/06C07K1/107
CPCC07K1/04C07K1/06C07K1/107Y02P20/55
Inventor 何春茂周仪陈永渌
Owner SOUTH CHINA UNIV OF TECH
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