Self-assembly short peptide and use thereof in antineoplastic medicine preparation

A technology for self-assembly of short peptides and drugs, applied in antitumor drugs, drug combinations, peptides, etc., can solve the problems of no in vivo animal experiments, weak killing effect, and weakened curative effect, and achieve obvious social and economic benefits. Good results

Inactive Publication Date: 2008-11-12
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the vast majority of anticancer drugs are in a state of free diffusion in the body. On the one hand, the drug cannot reach the concentration required for treatment in the lesion area, resulting in weakened efficacy; on the other hand, the free diffusion of anticancer drugs is bound to affect the body's Other normal tissues and organs cause certain side effects (see Sinha R, KimGJ, Nie S, & Shin DM (2006) Mol Cancer Ther 5, 1909-1917. LerouxJ-C, Allemann E, DeJaeghere F, Duelker E & Gurny R.( 1996) J Control Release 30, 339-50.)
[0005] In 2001, S

Method used

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  • Self-assembly short peptide and use thereof in antineoplastic medicine preparation
  • Self-assembly short peptide and use thereof in antineoplastic medicine preparation
  • Self-assembly short peptide and use thereof in antineoplastic medicine preparation

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0028] Example 1: Preparation of self-assembled short peptide R418

[0029] 1. Reagent

[0030]PyBOP (benzotriazol-1-yl-oxytripyrrolidinyl phosphorus hexafluorophosphate), Boc-Phe-Merrifield resin, hexahydropyridine, lutidine, TFA (trifluoroacetic acid), HPLC methanol, Protected amino acids (Fmoc-Lys(Boc)-OH, Fmoc-Ala-OH, Fmoc-Leu-OH, Fmoc-His(Trt)-OH, Fmoc-Phe-OH, Fmoc-Pro-OH, Fmoc-Ile-OH , Fmoc-Trp-OH, Fmoc-Gly-OH, Fmoc-Asp(OtBu)-OH, Fmoc-Arg(Pmc)-OH.IPE), thioanisole (anisole), EDT (ethylene dithiol), TIS (Methyl ethyl sulfide) and HOBT (1-hydroxybenzotriazole) are products of Merck; DMF (dimethyl formamide) is a product of South Korea's Samsung; NMM (methyl Maffein) is purchased from Sigma; DCM (two Chloromethyl), phenol, and triethylamine are products of China National Pharmaceutical (Group) Shanghai Chemical Reagent Company; methanol is a product of Shanghai Zhenxing Chemical No. 1 Plant; tetrahydrofuran is a product of Shanghai Chemical Reagent Station Central Chemical Plan...

Example Embodiment

[0052] Example 2: High performance liquid chromatography and mass spectrometry detection of self-assembled short peptide R418

[0053] The self-assembled short peptide R418 prepared in Example 1 was detected by high performance liquid chromatography (HPLC) (detection conditions: Phase A: 5% acetonitrile + 0.1% trifluoroacetic acid; Phase B: 95% acetonitrile + 0.1% Trifluoroacetic acid; the linear gradient is 20 minutes), see the test results figure 1 ,according to figure 1 The peak area in, confirms that its purity has reached 95%.

[0054] The self-assembled short peptide R418 prepared in Example 1 was detected by mass spectrometry (Finnigan LCQ mass spectrometer), and the test results are shown in figure 2 ,according to figure 2 It can be determined that its molecular weight is 4344.9 (theoretical molecular weight is 4344.11), indicating that the synthesized short peptide is indeed the designed peptide.

Example Embodiment

[0055] Example 3: Three-dimensional molecular model and self-assembly model rendering of R418 anti-tumor self-assembled short peptide

[0056] For the self-assembled short peptide R418 prepared in Example 1, the professional Molsoft.ICM drawing software was used to draw a schematic diagram of a three-dimensional molecular model based on the principle of energy minimization. For the schematic diagram of the drawn three-dimensional molecular model, see image 3 A. Through the schematic diagram, the spatial distribution of its amino acids can be clearly known. The schematic diagram shows that the anti-tumor active peptide S18 is located at the C-terminus of the self-assembled peptide RADA16-I, and the two are connected by a connecting region.

[0057] The self-assembled short peptide R418 prepared in Example 1 can form self-assembled nanofibers in water. For the self-assembled nanofibers formed by the self-assembled short peptide R418, professional Molsoft.ICM drawing software is use...

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Abstract

A self-assembly short peptide R418 consists of an anti-tumor bioactive peptide section S18, a self-assembly peptide section RADA16-I and a connection peptide section, and the amino acid sequence is described in sequence table SEQ ID NO.1. The characterizations of an atomic force microscope and a transmission electron microscope prove that R418 molecule has the characteristic of forming nano fiber through self assembly in a solution. In vitro cell experiment shows that the self-assembly short peptide R418 can remarkably cause the death of tumor cells K562, Jurkat and MDA-MB-435S and has lower cytotoxicity on NIH3T3 cell. Beastie living body imaging experiments show that: after self assembly, the holding time of the local concentration of the R418 in an in vivo tumor region is much longer than the holding time of the local concentration of the S18. In accordance with beastie living body imaging experiments, animal tumor inhibition experiments show that: the self-assembly short peptide R418 has better tumor inhibition effect as compared with short peptide S18.

Description

technical field [0001] The invention belongs to the field of self-assembled short peptides, in particular to a self-assembled short peptide and its application in preparing antitumor drugs. Background technique [0002] Self-assembled short peptides are a new type of nano-biological material. Since its appearance in the 1990s, it has received extensive attention and has been developed rapidly. A variety of self-assembled short peptides with different structures have been synthesized, and they can be used in cells. Three-dimensional culture and preparation of hydrophobic drug carriers, hemostatic drugs, burn treatment drugs, antibacterial drugs, etc. However, the preparation of more self-assembled short peptides and the expansion of the application range of self-assembled short peptides are still issues of concern to scientific and technological workers. [0003] Cancer is one of the major diseases affecting human health. About seven million patients die of cancer every year...

Claims

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Application Information

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IPC IPC(8): C07K14/00A61K38/16A61P35/02A61P35/00
Inventor 赵晓军唐成康
Owner SICHUAN UNIV
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