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Gramicidin, isomer thereof and application thereof

A short peptide and structural formula technology, applied in the field of its isomers and short peptides, can solve the problems of limiting biological activity and concentration drop

Inactive Publication Date: 2012-07-04
FOURTH MILITARY MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Although ang1-7 has very significant anti-cardiovascular and cerebrovascular disease characteristics, after it enters the human body, it is rapidly degraded under the action of various enzymes in the body, and its concentration is greatly reduced, which greatly limits its biological activity.

Method used

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  • Gramicidin, isomer thereof and application thereof
  • Gramicidin, isomer thereof and application thereof
  • Gramicidin, isomer thereof and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Implementation 1 The enzymolysis resistance effect of short peptides of the present invention and its isomers compared to angiotensin 1-7

[0043] Dissolve angiotensin 1-7, inventive short peptide 1, and inventive short peptide 2 to 5 mmol / L with PBS.

[0044] Use PBS to dissolve angiotensin 1-7, inventive short peptide 1, and inventive short peptide 25 μl + 20 μl PBS in a 37°C water bath for 30 minutes + 5 μl acetonitrile for standard spectra by HPLC.

[0045] Invention short peptide 15μl + 10μl ACE or NEP or LAP enzyme (0.05U) + 10PBS 37°C water bath for 30min + 5μl acetonitrile for HPLC.

[0046] Invention short peptide 25 μl + 10 μl ACE or NEP or LAP enzyme (0.05 U) + 10PBS 37°C water bath for 30 min + 5 μl acetonitrile for HPLC.

[0047] Chromatographic conditions

[0048] Liquid A: 0.1% phosphoric acid solution

[0049] Solution B: 100% acetonitrile solution

[0050] C 18 column

[0051] Flow rate: 0.35ml / min

[0052] After equilibrating the column with 12%...

Embodiment 2

[0054] Example 2 Short peptides of the present invention and their isomers stimulate HUVEC to release nitric oxide

[0055] Digest HUVEC cells with 2×10 per well 5 Cells were plated into a 12-well plate and added with 10% FBS DMEM at 37°C 5% CO 2 Incubate overnight.

[0056]Take 10% FBS DMEM to dilute ang1-7 and the short peptide of the present invention respectively, its structural formula is Ac-Asp-Arg-Val-Tyr-Ile-His-Pro-NH 2 , and Ac-Asp-Arg-Val-Tyr(D)-Ile-His(D)-Pro-NH 2 , is 1μm / L. The 12 wells were divided into drug-free group, ang1-7, short peptide 1 of the present invention, and short peptide 2 of the present invention. Two sub-wells in each of the four groups absorbed the culture solution, added 900 μl of fresh medium or drugs, and incubated at 37°C for 30 minutes.

[0057] Take out the 12-well plate and take 50 μl of culture solution from each well to measure the content of nitric oxide.

[0058] see results figure 2 , as shown in the figure, after adding the...

Embodiment 3

[0059] Example 3 Short peptides of the present invention and their isomers inhibit tubule formation in HUVEC cells

[0060] Pre-cool the 96-well plate and 200μl pipette tips, and melt the matrgiel matrigel stored at -20℃ overnight at 4℃.

[0061] Quickly add 50 μl of melted matrgiel per well to a pre-cooled 96-well plate, and place at room temperature for 10 minutes until the matrgiel solidifies.

[0062] Digest HUVEC cells to adjust the cell density to 2×10 5 144 μl of cell suspension was added to solidified matrgiel.

[0063] DMEM deployment 1μm / L ang1-7, short peptide 1 of the present invention, short peptide 2 of the present invention, 16 wells were divided into four groups: no drug group, ang1-7, short peptide 1 of the present invention, short peptide 2 of the present invention, each group 3 Add 16 μl of drug solution to each auxiliary well in the 96-well plate with cells added.

[0064] 37°C 5% CO 2 After culturing for 8 hours, the effect of tubule formation was obse...

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Abstract

The invention discloses gramicidin, isomer thereof and application thereof. The structure is Ac-Asp-Arg-Val-Tyr-Ile-His-Pro-NH2 and Ac-Asp-Arg-Val-Tyr(D)-Ile-His(D)-Pro. Two modified construction bodies have biological activity which is similar to angiotensin 1-7 and capable of promoting human umbilical vein endothelial cells (HUVEC) to release nitrogen oxide (NO) for migration, forming a tubelet and restraining A549 cell growth. Simultaneously, the modified construction bodies have degradation capability of three degradation enzymes including ACE, NEP and AP, thereby ensuring that the modified construction bodies have longer half-life periods than the angiotensin 1-7. The modified construction bodies are simple to obtain and provide important application value for development of novel polypeptide drugs for treating cardiovascular and cerebrovascular diseases.

Description

technical field [0001] The present invention relates to a short peptide, its isomer and its application. In particular, the short peptide and its isomers are used as active ingredients to relax blood vessels, lower blood pressure, resist thrombosis, control arrhythmia and have anticancer effects. Background technique [0002] Aspartic acid-arginine-valine-tyrosine-isoleucine-histidine-proline (Asp-Arg-Val-Tyr-Ile-His-Pro), abbreviated as DRVYIHP, it It is an endogenous heptapeptide, also known as ang1-7, which is widely distributed in various tissues and body fluids in the body. This heptapeptide is mainly released by the hydrolysis of angiotensin II by angiotensin-converting enzyme 2, or a small amount of synthesis of angiotensinogen by other pathways. The concentration in blood is generally nanomolar. The pharmacokinetic study of ang1-7 found that ang1-7 was degraded quickly after intravenous injection into the body, with a half-life of only 8 to 12 seconds. ang1-7 is ...

Claims

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Application Information

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IPC IPC(8): C07K7/06A61K38/08A61P9/12A61P9/08A61P9/00A61P9/06A61P35/00A61P7/02A23L1/305
Inventor 张英起王增禄郭翰文黄同列
Owner FOURTH MILITARY MEDICAL UNIVERSITY
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