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

CN101302249AInactive Publication Date: 2008-11-12SICHUAN UNIV
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Patent Information

Authority / Receiving Office
CN · China
Current Assignee / Owner
Publication Date
2008-11-12
Estimated Expiration
Not applicable · inactive patent

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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.
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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...

Examples

Embodiment 1

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

[0029] 1. Reagents

[0030]PyBOP (benzotriazol-1-yl-oxytripyrrolidinylphosphonium 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 (thioanisole), EDT (ethanedithiol), TIS (methyl ethyl sulfide), HOBT (1-hydroxybenzotriazole) are products of Merck; DMF (dimethylformamide) is a product of Samsung, South Korea; NMM (methylmafeline) is purchased from Sigma; DCM (two Chloromethane), phenol, and triethylamine are products of China Pharmaceutical (Group) Shanghai Chemical Reagent Company; methanol is a product of Shanghai Zhenxing Chemical Factory No. 1; tetrahydrofuran is a product of Shanghai Chemical Reagent Station Central Chemical Fact...

Embodiment 2

[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 was 5% acetonitrile+0.1% trifluoroacetic acid; phase B was 95% acetonitrile+0.1% Trifluoroacetic acid; the linear gradient is 20 minutes), the test results are shown in figure 1 ,according to figure 1 The peak area in the spectrum confirmed that its purity reached 95%.

[0054] The self-assembled short peptide R418 prepared in Example 1 is detected by mass spectrometry (the mass spectrometer is Finnigan LCQ), and the detection 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.

Embodiment 3

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

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

[0057] The self-assembled short peptide R418 prepared in Example 1 can form self-assembled nanofibers in water, and the self-assembled nanofibers formed by the self-assembled short peptide R418 are drawn using professional Molsoft.ICM drawing software based on the prin...