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Polypeptide for inhibiting HIV infection and medicinal application thereof

A technology of derivatives and stereoisomers, applied in medical preparations containing active ingredients, peptide sources, applications, etc., to achieve the effects of enhancing antiviral activity, saving synthesis costs, and simplifying sequences

Inactive Publication Date: 2017-03-29
FUDAN UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

So far, there is still no effective vaccine available, so AIDS is still a major threat to human public health

Method used

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  • Polypeptide for inhibiting HIV infection and medicinal application thereof
  • Polypeptide for inhibiting HIV infection and medicinal application thereof
  • Polypeptide for inhibiting HIV infection and medicinal application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] Embodiment 1: the preparation of polypeptide

[0052] Synthetic polypeptide JLS1-JSL5 (in this example, synthesized by SynPeptide Co Ltd), was purified and identified by high performance liquid chromatography (HPLC) and mass spectrometry (PerSeptive Biosystems, Framingham, MA), showing that the sequence was correct and the purity was greater than 98%; molecular weight and purity of polypeptide of the present invention are as shown in table 1

[0053] Table 1. Molecular weight and purity of peptides

[0054]

[0055]

Embodiment 2

[0056] Example 2: Polypeptide inhibits HIV-infected cells

[0057] 2.1 Experimental materials and methods

[0058] 2.1.1 The method for detecting the activity of C polypeptide in inhibiting HIV-1X4 strain IIIB infection of MT-2 cells is as follows: add 50 μL of IIIB virus (diluted with serum-free 1640) and 50 μL of doubling-diluted (4-fold) to each well of a 96-well plate C polypeptide (diluted with serum-free 1640), incubated at 37°C for 30 minutes, then added 100 μL of cells (10 5 cells / ml, diluted with 1640 culture medium with 10% serum), the wells that only added the same final concentration of MT-2 cells were used as negative controls, and the wells that added the same final concentration of IIIB virus and MT-2 cells were not used. The well where the drug was added was the positive control; on the second day, 150 μL of the supernatant was aspirated from each well, and 150 μL of fresh 1640 culture solution containing 10% serum was added; on the fifth day, 50 μL of the sup...

Embodiment 3

[0063] Example 3. Broad-spectrum anti-HIV effect of JLS2 and JLS5

[0064] The retrovirus of HIV is prone to genome mutations, the present invention selects JSL2 and JSL5, which have better effects on laboratory-adapted strains, and detects their antiviral activity to a series of clinical strains; clinical strains can be divided into many subtypes, including A-D, F-H, J and K subtypes, etc. In this experiment, SC26EK was used as a control to observe the effect of its N-terminal and C-terminal plus enhanced sequences. At the same time, T20, the only fusion inhibitor currently on the market, and The fusion inhibitor HP23 with the highest antiviral activity reported now is used as a positive control;

[0065] The method is as follows: add 50 μL of HIV virus (diluted with serum-free 1640) and 50 μL of double-diluted (4-fold) C polypeptide (diluted with serum-free 1640) to each well of a 96-well plate, incubate at 37°C for 30 minutes, and then add 100 μL cells (10 5cells / ml, dilu...

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Abstract

The invention belongs to the field of biological medicine and relates to an anti-HIV infection peptide, in particular to a polypeptide shown by a formula 1 CP_I(L)_D_I (L), its derivatives, its stereoisomers, or its salts free of physiological toxicity. CP in the formula represents a C-terminal polypeptide derived from HIV-1 gp41 and having HIV-1 inhibiting activity, L represents leucine, I represents isoleucine, and D represents aspartic acid. Variable amino acid is added to the carbon terminal of the C-terminal polypeptide having the HIV-1 inhibiting activity to obtain a longer polypeptide, so that the polypeptide has remarkable strengthened antiviral activity. The invention further relates to a drug composition containing the polypeptide shown by the formula 1, its derivatives, its stereoisomers or its salts free of physiological toxicity and application in preparation of drugs for treating or preventing related diseases caused by HIV infection, especially acquired immune deficiency syndrome.

Description

technical field [0001] The invention belongs to the field of biomedicine, and relates to anti-HIV infection polypeptides; specifically, formula 1: CP-I(L)-D-I(L), polypeptides represented by formula 1, derivatives thereof, stereoisomers thereof, or Its non-physiologically toxic salts. The polypeptide can significantly improve the activity of the original C-terminal polypeptide in inhibiting HIV infection. The present invention also relates to a pharmaceutical composition containing the above-mentioned polypeptide of formula 1, its derivative, its stereoisomer, or its non-physiologically toxic salt, and the formula 1 polypeptide, its derivative, its stereoisomer, or its Use of the non-physiologically toxic salt in the treatment or prevention of related diseases caused by HIV infection, especially acquired immunodeficiency syndrome (AIDS). Background technique [0002] According to reports, human acquired immunodeficiency syndrome, namely AIDS (AIDS), has always been a hot s...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/16A61K38/16A61P31/18C12N15/49
CPCA61K38/00C07K14/005C12N2740/16222
Inventor 姜世勃陆路苏珊张荣光叶盛朱赟
Owner FUDAN UNIV
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