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Peptide which can induce antibody capable of recognizing stereostructure of HIV

A three-dimensional structure, peptide-inducing technology, applied in the direction of antibody medical components, peptides, peptide sources, etc., can solve the problems of not showing anti-HIV activity, not reaching clinical application, etc.

Inactive Publication Date: 2014-01-08
NAT UNIV CORP TOKYO MEDICAL & DENTAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the significant variability of the HIV genome, although the above-mentioned antibodies show anti-HIV activity for a certain HIV strain, they do not show anti-HIV activity for other strains, so they have not yet reached clinical application.

Method used

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  • Peptide which can induce antibody capable of recognizing stereostructure of HIV
  • Peptide which can induce antibody capable of recognizing stereostructure of HIV
  • Peptide which can induce antibody capable of recognizing stereostructure of HIV

Examples

Experimental program
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preparation example Construction

[0072] The method for synthesizing the HIV stereostructure-recognizing antibody-inducing peptide of the present invention (hereinafter, also simply referred to as "the method of synthesizing the peptide of the present invention") includes a method for synthesizing an HIV stereostructure-recognizing antibody-inducing peptide that recognizes the trimer region of C34 , is characterized in that it includes the following steps: a step of synthesizing a derivative of the helical region C34 peptide on the C-terminal side of the transmembrane protein gp41 of HIV particles (hereinafter also simply referred to as "C34 peptide derivative"); and by A template compound with C3 symmetry with three equivalent linker structures (hereafter, simply referred to as "template compound in the present invention") is combined with the above-mentioned C34 peptide derivative to synthesize a trimerization of the C34 peptide derivative body process.

[0073]The C34 peptide derivative in the present inven...

Embodiment 1

[0105] [Design and synthesis of C34 peptide derivative trimer]

[0106] (1) Design of C34 peptide derivative trimer

[0107] The target antigen molecule C34 peptide derivative trimer is designed as follows, that is, a peptide (C34 peptide derivative) that mimics the C34 peptide is synthesized separately in a template compound containing three peptides, and they are combined ( Figure 7 ). The C34 peptide is considered to interact with the N36 peptide from the N-terminal side of the C34 peptide when forming a 6-helical bundle with the N36 peptide. Therefore, it was presumed that an antibody that recognizes the N-terminal side region of the C34 peptide is important in order to induce antibodies that inhibit HIV membrane fusion at an earlier stage. Therefore, in order to maintain the N-terminal side region of the C34 peptide in a more natural state, the C-terminal side of C34 was set as the binding site for the C3 symmetric template compound ( Figure 7 ).

[0108] (2) Design...

Embodiment 2

[0133] [Two-dimensional structure analysis of C34 peptide derivative trimer]

[0134] In order to analyze the two-dimensional structure of the C34 peptide derivative trimer, the measurement of circular dichroism (CD) spectrum was carried out. Specifically, it was carried out by the following method. The C34 peptide derivative trimer (final concentration: 2 μM) obtained in Example 1 above was dissolved in PBS (50 mM sodium phosphate, 150 mM NaCl, pH 7.2). The solution was fixed in a J-720 circular dichroic spectrometer (manufactured by JASCO) equipped with a temperature regulator, and the wavelength dependence of the molar ellipticity [θ] was observed at 25° C. at 195 to 250 nm. Also, instead of the C34 peptide derivative trimer (final concentration 2 μM), the C34 peptide derivative monomer (C34 derivative 2) (final concentration 6 μM) obtained in Example 1 above was used to measure the CD spectrum in the same manner. Figure 14 (A) shows its result.

[0135] CD spectrum of ...

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Abstract

The purpose of the present invention is to provide a peptide which can induce an excellent or novel neutralizing antibody against an HIV, and thereby prevent or treat HIV infection or expand choices of the prevention or treatment. A means for achieving the purpose is characterized by using a peptide which can induce an antibody capable of recognizing the stereostructrue of an HIV, wherein the peptide can recognize a trimeric region in C34 and is characterized in that three molecules of a derivative of a helical region C34 peptide located on the C-terminal side of a transmembrane protein gp41 of an HIV particle are bound together through a template compound that has three equivalent linker structures in a C3 symmetric manner.

Description

technical field [0001] The present invention relates to a peptide that induces an antibody that recognizes the three-dimensional structure of HIV (Human Immunodeficiency Virus: Human Immunodeficiency Virus), its synthesis method, and HIV that uses the three-dimensional structure of HIV induced by the peptide or the peptide as an active ingredient. Preventive and / or therapeutic agents for infectious diseases. In particular, it relates to the formation of a hexamer of the helical regions C34 and N36 on the C-terminal side of the transmembrane protein gp41 of the HIV particle of the HIV vaccine as a mechanism of invasion into the target cell of HIV, by acting on the helical region C34 The trimer region of gp41 hinders the formation of hexamers of C34 and N36 of gp41, and prevents the invasion of HIV target cells from the antibody-induced peptide that recognizes the HIV stereostructure, its synthesis method, and the HIV stereo that is induced by the peptide A prophylactic and / or ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/155A61K39/21A61P31/18C07K1/06
CPCC07K1/13A61K39/21A61K47/48215C12N2740/16011C07K14/005A61K39/00C12N2740/16122C12N2740/16134A61K39/12A61K47/60A61P31/18A61P37/04C07K14/155
Inventor 玉村启和鸣海哲夫野村涉桥本知惠驹野淳宫内浩典
Owner NAT UNIV CORP TOKYO MEDICAL & DENTAL UNIV
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