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Polypeptide for inhibiting hiv, pharmaceutical composition and use thereof

A composition and drug technology, applied in the field of its pharmaceutical composition and HIV-inhibiting polypeptide, can solve the problems of short sequence and high synthesis cost

Inactive Publication Date: 2016-09-14
INST OF PHARMACOLOGY & TOXICOLOGY ACAD OF MILITARY MEDICAL SCI P L A
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Although there is a fusion inhibitor T20 on the market and other fusion inhibitors such as Sifuvirtide (CN1334122) in clinical research, due to the rapid emergence of drug-resistant virus strains, the development of fusion inhibitors for resistant viruses has become a top priority
At the same time, since the currently obtained highly active polypeptide fusion inhibitors are all polypeptides with about 36 amino acid residues, their synthesis costs are relatively high, so it is of great significance to obtain polypeptide drugs with shorter sequences and high anti-HIV activity

Method used

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  • Polypeptide for inhibiting hiv, pharmaceutical composition and use thereof
  • Polypeptide for inhibiting hiv, pharmaceutical composition and use thereof
  • Polypeptide for inhibiting hiv, pharmaceutical composition and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0127] Example 1: Preparation of polypeptide 1

[0128] Standard Fmoc solid-phase peptide synthesis method is used. All polypeptide sequences are amidated at the C-terminus and acetylated at the N-terminus in accordance with the conventions of polypeptide synthesis (persons in the art know that these modifications have no fundamental impact on polypeptide activity). Choose RinkAmide resin, and peptides extend from C-terminal to N-terminal. Condensing agent is HBTU / HOBt / DIEA. The deprotection agent is piperidine / DMF solution. The lysing agent is TFA, and the crude peptide is dissolved in water and lyophilized for storage. Separation and purification by medium pressure liquid chromatography or HPLC, pure peptide content> 95%. Matrix-assisted laser analysis time-of-flight mass spectrometry (MALDI-TOF-MS) determines the molecular weight of peptides.

[0129] The conditions for microwave peptide synthesis are as follows:

[0130] Amino acid: 0.2M DMF solution; activator: 0.45M HBTU...

Embodiment 2－12

[0137] Example 2-12: Preparation of polypeptide 2-12

[0138] The preparation was carried out with reference to the method in Example 1. The specific amino acid sequences are shown in Table 1 respectively. Its molecular weight and purity are shown in Table 2 above.

Embodiment 13

[0140] Example 13: Detection of anti-HIV-1 cell-cell fusion activity of polypeptide

[0141] The inventors used HIV-1 Env-mediated cell-cell fusion model to determine the activity of the designed polypeptide. The target cells are TZM-bl cells (provided by NIH AIDS Reagents and Reference Projects in the United States, catalog number 8129), which express CD4 T-cell receptors and chemokine co-receptors CCR5 and CXCR4 on their surface, which can be recognized by HIV-1Env. At the same time, the luciferase reporter gene is also transcribed in the cell, but does not contain the promoter of this gene, so the background expression of luciferase in a single cell is very low. The effector cells are HL2 / 3 cells (provided by NIH AIDS Reagents and Reference Project, catalog number 1294), which express HIV-1 Env on the surface, and Env attacks the target cells to complete cell fusion. At the same time, the luciferase report is also transcribed in the cell The promoter of the gene. The two ki...

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Abstract

Disclosed are a polypeptide for use in inhibiting the HIV, a pharmaceutical composition comprising the polypeptide, and a use thereof. The polypeptide comprises the sequence as expressed by SEQ ID NO: 8 or by SEQ ID NO: 9. The polypeptide comprise neither a pocket-binding domain nor a lipid membrane-binding domain generally recognized as necessary for high activity polypeptide fusion inhibitors, and the polypeptide is of a reduced length, but the polypeptide exhibits an increased anti-HIV activity.

Description

Technical field [0001] The invention belongs to the field of biomedicine, and relates to a polypeptide for inhibiting HIV, its pharmaceutical composition and its use. Background technique [0002] Human immunodeficiency virus type 1 (HIV-1) is the causative agent of AIDS. There are currently more than 30 million infected people worldwide, causing about 2 million deaths each year, and about 2 million new infections each year, which seriously threatens human health. [0003] HIV-1 infects host cells through its envelope glycoprotein (Env)-mediated virus-cell membrane fusion. Env contains surface subunit gp120 and transmembrane subunit gp41. Three Envs form a non-covalent complex embedded on the surface of the virus. The surface subunit gp120 is responsible for molecular recognition in the process of virus-infected cells to find and approach the target cell. At the same time, it plays the role of stabilizing the transmembrane subunit gp41, and releases gp41 at an appropriate time to ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K14/16C12N15/49C12N15/63C12N1/19C12N1/21C12N5/10A61K38/16A61P31/18
CPCA61K38/00C07K14/005C12N2740/16022A61P31/18
Inventor 蔡利锋刘克良王昆郑保华
Owner INST OF PHARMACOLOGY & TOXICOLOGY ACAD OF MILITARY MEDICAL SCI P L A
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