CN108640977A - Specifically bind the polypeptide of envelope glycoprotein gp120 and its application on HIV - Google Patents
Specifically bind the polypeptide of envelope glycoprotein gp120 and its application on HIV Download PDFInfo
- Publication number
- CN108640977A CN108640977A CN201810625599.6A CN201810625599A CN108640977A CN 108640977 A CN108640977 A CN 108640977A CN 201810625599 A CN201810625599 A CN 201810625599A CN 108640977 A CN108640977 A CN 108640977A
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- polypeptide
- hiv
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- AIDS & HIV (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Peptides Or Proteins (AREA)
Abstract
The polypeptide of albumen gp120 and its application on a kind of specific binding inhibition of HIV.The first step that inhibition of HIV infects T cell is that the gp120 of virus surface is combined with the CD4 equimoleculars on T cell surface, and invention synthesis gp120 bonding agents can effectively infect blocking virus, to protect T cell, therefore be of great significance.Core polypeptide of the present invention：Gln Ile Lys Ile Leu Gly Asn Gln Gly Ser Phe Leu Thr Asp Gly Pro, molecular weight 1687.91.Such polypeptide can specifically bind gp120, and have the dissociation constant of very little（10‑9M）, the development of the control AIDS state of an illness is had potential application.
Description
Technical field
The present invention relates to the polypeptide of albumen gp120 on specific binding inhibition of HIV a kind of and its applications.
Background technology
The duplication of inhibition of HIV can probably be divided into following six step：1）Inhibition of HIV by envelope glycoprotein gp120 and
The receptors such as the CD4 on target cell are combined into cell；2）The DNA of the reverse transcriptase reverse transcription synthesis of virus itself is integrated into host
On the genome of cell；3）The process for starting transcription synthesizes new mRNA；4）Transcript mRNA synthesizes new virus protein；5）Assembling
New virion；6）The albumen and particle maturation of release new assembling.One in above six steps of cut-out can control
Virus infects, and to reduce internal viral level, controls the development of the AIDS state of an illness.
The design of current drug mainly has inhibition reverse transcriptase（Step 2）, inhibit integrase（Step 2）With inhibition albumen
Enzyme（Step 4）Equal several methods.But these types of method is clinically easy induction HIV resistance mutations, and have to human body
Larger side effect, to limit their uses clinically.Therefore the drug for researching and developing new AntiHIV1 RT activity, is especially turned off disease
Malicious route of entry（Step 1）It is particularly important.
Polypeptide drugs have many advantages, such as that action site is single-minded, curative for effect, less toxic and easy preparation.T-20 is on currently the only
City AntiHIV1 RT activity film fusion polypeptide drugs, but this drug there are solubility it is low, expensive the problems such as.Therefore develop a kind of
Simpler, solubility is good, and the polypeptide AntiHIV1 RT activity polypeptide drug of high specificity is very necessary.
Invention content
The purpose of the present invention is to provide the polypeptides of albumen gp120 on specific binding inhibition of HIV a kind of.
A kind of polypeptide, it is characterised in that the polypeptide is A）Or B）Any polypeptide：
A）For the polypeptide of amino acid sequence shown in SEQ ID NO.1；
B）Substitution and/or missing of the amino acid residue sequence shown in SEQ ID NO.1 by one or several amino acid residues
And/or addition and/or extend and with HIV-resistant activity by A）Derivative polypeptide.
A kind of application of above-mentioned polypeptide in the drug for preparing anti-HIV-1；
A kind of above-mentioned polypeptide prepares the application in the drug for the treatment of or prevention AIDS caused by HIV-1.
Polypeptide in the present invention is synthesized by polypeptide company, other particular/special requirements are had no.
Polypeptide of the present invention includes polypeptide sequence shown in sequence 1：Gln-Ile-Lys-Ile-Leu-Gly-Asn-
Gln-Gly-Ser-Phe-Leu-Thr-Asp-Gly-Pro, molecular weight 1687.91.After synthesis polypeptide, through high-efficient liquid phase color
After spectrum and mass-spectrometric technique verification, show that the substrate of synthesis is 1 polypeptide of complete sequence.
Pass through surface plasma resonance technology（SPR, Biacore T200）Polypeptide in the detection present invention and gp120 eggs
In vain, the combination of BSA albumen and CD4 albumen, it was demonstrated that the polypeptide in the present invention only has specific recognition effect to gp120, sees
Attached drawing 1.Use surface plasma resonance technology（SPR, Biacore T200）Polypeptide in the detection present invention and gp120 albumen
Association and dissociation dynamics is shown in attached drawing 2, and the dissociation constant of the two is 7.50 × 10-9 M。
The biological characteristics performance of polypeptide provided by the present invention predicts its many application.Most importantly pass through polypeptide and HIV
In virus gp120 in conjunction with and prevent gp120 from being combined with the CD4 on target cell, to control the development of the AIDS state of an illness, have latent
Application value.
Description of the drawings
Fig. 1 is that polypeptide provided by the present invention specifically binds performance with protein gp120.
Fig. 2 is the dynamic performance that polypeptide provided by the present invention is combined with protein gp120.
Specific implementation mode
Embodiment is given below so that the invention will be further described.It is necessarily pointed out that following embodiment cannot
Be interpreted as limiting the scope of the invention, if the person skilled in the art in the field according to aforementioned present invention content to this hair
It is bright to make some nonessential modifications and adaptations, such as small mutation is carried out to the polypeptide portion amino acid sequence of design, still
Belong to the scope of the present invention.
Embodiment 1：
1, the present invention in polypeptide preparation
In the amino acid sequence of polypeptide such as sequence table shown in SEQ ID NO.1, by Peptide systhesis, company synthesizes.
2, polypeptide and protein gp120 specifically bind performance in the present invention
In order to prove the specific binding performance of polypeptide and protein gp120 designed in the present invention, surface plasma is used
Resonance technique（SPR, Biacore T200）Polypeptide in the detection present invention and gp120 albumen, the knot of BSA albumen and CD4 albumen
Cooperation is used.This three kinds of albumen are coupled at the different channels of SPR chips, and polypeptide flows through this three in a concentration of 1 μM of the present invention
Channel, the results showed that the polypeptide in the present invention only has specific recognition combination to gp120, sees attached drawing 1.
3, polypeptide and protein gp120 binding forces measure in the present invention
In order to prove that the polypeptide in the present invention and protein gp120 have very strong binding ability, surface plasma resonance skill is used
Art（SPR, Biacore T200）Detection the present invention in polypeptide and gp120 albumen association and dissociation dynamics, polypeptide it is dense
Degree gradient is set as 50 nM, 250 nM, 500 nM, 1000 nM.The result shows that the dissociation constant of the two is 7.50 × 10-9M,
Show that polypeptide and albumen gp120 have very strong binding force, sees attached drawing 2.
Sequence table
<110>Shanghai University
<120>Specifically bind the polypeptide of envelope glycoprotein gp120 and its application on HIV
<160> 1
<170> SIPOSequenceListing 1.0
<210> 1
<211> 48
<212> RNA
<213>Artificial sequence ()
<400> 1
Claims (3)
1. a kind of polypeptide, it is characterised in that the polypeptide is A）Or B）Any polypeptide：
A）For the polypeptide of amino acid sequence shown in SEQ ID NO.1；
B）Substitution and/or missing of the amino acid residue sequence shown in SEQ ID NO.1 by one or several amino acid residues
And/or addition and/or extend and with HIV-resistant activity by A）Derivative polypeptide.
2. a kind of application of polypeptide according to claim 1 in the drug for preparing anti-HIV-1.
3. a kind of polypeptide according to claim 1 is prepared in the drug for treating or preventing the AIDS caused by HIV-1
Using.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810625599.6A CN108640977A (en) | 2018-06-18 | 2018-06-18 | Specifically bind the polypeptide of envelope glycoprotein gp120 and its application on HIV |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810625599.6A CN108640977A (en) | 2018-06-18 | 2018-06-18 | Specifically bind the polypeptide of envelope glycoprotein gp120 and its application on HIV |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108640977A true CN108640977A (en) | 2018-10-12 |
Family
ID=63752643
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810625599.6A Pending CN108640977A (en) | 2018-06-18 | 2018-06-18 | Specifically bind the polypeptide of envelope glycoprotein gp120 and its application on HIV |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108640977A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108640978A (en) * | 2018-06-20 | 2018-10-12 | 上海大学 | Specifically bind the polypeptide of albumen gp120 and its application on inhibition of HIV |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1303394A (en) * | 1998-06-20 | 2001-07-11 | 美国联合生物医学公司 | Peptide compound for preventing and treating HIV infection and immunity diseases |
| CN1487951A (en) * | 2001-01-23 | 2004-04-07 | ����ԭ����ίԱ�� | Peptides having affinity for the GP 120 viral protein and use thereof |
| US20060084593A1 (en) * | 2002-04-19 | 2006-04-20 | Commissariat A L'energie Atomique | Anti-hiv composition, production method thereof and medicament |
| CN1809381A (en) * | 2003-06-12 | 2006-07-26 | 瓦克斯根公司 | HIV-1 envelope glycoproteins having unusual disulfide structure |
-
2018
- 2018-06-18 CN CN201810625599.6A patent/CN108640977A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1303394A (en) * | 1998-06-20 | 2001-07-11 | 美国联合生物医学公司 | Peptide compound for preventing and treating HIV infection and immunity diseases |
| CN1487951A (en) * | 2001-01-23 | 2004-04-07 | ����ԭ����ίԱ�� | Peptides having affinity for the GP 120 viral protein and use thereof |
| US20060084593A1 (en) * | 2002-04-19 | 2006-04-20 | Commissariat A L'energie Atomique | Anti-hiv composition, production method thereof and medicament |
| CN1809381A (en) * | 2003-06-12 | 2006-07-26 | 瓦克斯根公司 | HIV-1 envelope glycoproteins having unusual disulfide structure |
Non-Patent Citations (4)
| Title |
|---|
| MARI A SCARSELLI 等: "The Design of a Specific Ligand of HIV gp120", 《JOURNAL OF PEPTIDE SCIENCE》 * |
| 余勇 等: "一种新型多肽类HIV-1进入抑制剂", 《科学通报》 * |
| 夏承来 等: "HIV包膜蛋白 的结构及其相应的病毒进入抑制剂", 《中国药理学通报 》 * |
| 李建辉: "HIV对CD4+T细胞亚群的损伤及表位疫苗的免疫原性测定", 《中国学位论文全文数据库》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108640978A (en) * | 2018-06-20 | 2018-10-12 | 上海大学 | Specifically bind the polypeptide of albumen gp120 and its application on inhibition of HIV |
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| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20181012 |