Mitochondria targeted membrane-permeable cyclopeptide as well as preparation method and use thereof

A mitochondrial and targeting technology, which is applied in the preparation method of peptides, chemical instruments and methods, peptides, etc., can solve the problems that mitochondrial targeting peptides are not easy to modify, and achieve the effect of good membrane permeability and membrane penetration ability

Inactive Publication Date: 2019-12-31
合肥修合生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The present invention aims at the disadvantage that mitochondrial targeting peptides are not easy to modify, and

Method used

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  • Mitochondria targeted membrane-permeable cyclopeptide as well as preparation method and use thereof
  • Mitochondria targeted membrane-permeable cyclopeptide as well as preparation method and use thereof
  • Mitochondria targeted membrane-permeable cyclopeptide as well as preparation method and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0019] Embodiment 1: synthetic hydrazide resin

[0020] Swell 2-Cl-Trt-Cl resin (200mg) with DMF (2ml), add dropwise the mixture of DIEA (266ul), hydrazine hydrate (80ul) and DMF (800ul) under ice-bath stirring, and stir in ice-bath for 20min After the system was stirred at room temperature for 70 min, 40 ul of methanol was added to terminate the reaction. Transfer the obtained hydrazide-Trt(2-Cl) resin to a sand core funnel, wash thoroughly with DMF, MeOH, and diethyl ether for 3-5 times in sequence, and place the resin in a vacuum dryer for 1 h.

Embodiment 2

[0021] Embodiment 2: Solid-phase synthesis of hydrazide polypeptide by Fmoc method

[0022] The synthetic sequence is: Boc-C(Trt)-K(Alloc)-r(Pbf)-Cha-r(Pbf)-Cha-r(Pbf)-NH-NH 2

[0023] 1. Add hydrazide-Trt (2-Cl) resin 50mg (20umol) into the solid phase reactor and swell with DMF for 15min.

[0024] 2. Now prepare the DMF mixed solution of Oxyma, DIC and Fmoc-D-r(pdf)-OH (Oxyma (12.6mg, 4.5 equivalent): DIC (14ul, 4.5 equivalent): Fmoc-D-r(pdf)-OH (58.4mg, 4.5 equivalents), dissolved in 400 mL of DMF), was added into the reactor, and reacted at 55° C. for 40 min. After the reaction, the obtained resin was washed with DMF for 3-5 times.

[0025] 3. Add an appropriate amount of blocking reagent (acetic anhydride: 2,6-lutidine: DMF=5:6:89) to the reaction system to react for 3 minutes, block unreacted amino acids, and wash the obtained resin 3-5 times with DMF again ;

[0026] 4. Add the resin obtained in step 3 into the DMF solution containing 20% ​​piperidine and process it...

Embodiment 3

[0029] Embodiment 3: Resin polypeptide Alloc protecting group deprotection

[0030]Weigh 24mg of Pd(PPh3)4 (20.8umol), 60ul of N-methylaniline (554.4umol) and dissolve in 1.2mL of THF, mix well, inhale into the resin peptide obtained in Example 2, and react at room temperature in the dark for 2 hours; After the reaction is over, use DMF (3mL×3) and 0.5% NaS prepared by DMF in turn 2 CN(C 2 h 5 ) 2 (3mL×6), DCM (3mL×3), DMF (3mL×3) washed the resin until the dark brown color disappeared.

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Abstract

The invention discloses a mitochondria targeted membrane-permeable cyclopeptide as well as a preparation method and a use thereof, wherein the structure of a mitochondria targeted peptide is as follows: the mitochondria targeted membrane-permeable cyclopeptide can be specific to targeting cell mitochondria, and a confocal inverted fluorescence microscopic imaging experiment shows that the structure has good membrane permeability to Hela cells, and the colocalization coefficient Pr of the structure and a commercial mitochondrial dye is equal to 0.74, and the structure can be efficiently targeted and localized to mitochondria.

Description

technical field [0001] The invention relates to the chemical synthesis of a mitochondrial-targeted membrane-penetrating cyclic peptide and the application of the mitochondrial-targeted membrane-penetrating cyclic peptide in the delivery of active substances. Background technique [0002] The main function of mitochondria is to efficiently convert the energy stored in organic matter into direct energy for cell life activities for the needs of cell life activities. As the main place of animal cell respiration, mitochondria have the reputation of "power factory". Mitochondria play a vital role in maintaining the normal activities of cells. Mitochondria are involved in multiple aspects of cellular life processes, including cellular physiology, reactive oxygen species production, calcium homeostasis, and programmed cell apoptosis. Abnormal mitochondrial function is closely related to the occurrence of many diseases, such as: brain necrosis, cardiomyopathy, tumor, infertility, P...

Claims

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Application Information

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IPC IPC(8): C07K7/64C07K1/04C07K1/06A61K47/64A61P35/00G01N21/64
CPCA61K47/64A61P35/00C07K7/64G01N21/6486Y02P20/55
Inventor 孟祥明杨倩倩方葛敏朱满洲
Owner 合肥修合生物科技有限公司
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