EP0654080A1 - PEPTIDES IMITANT LE DETERMINANT ANTIGENIQUE DE gp120 DE HIV - Google Patents
PEPTIDES IMITANT LE DETERMINANT ANTIGENIQUE DE gp120 DE HIVInfo
- Publication number
- EP0654080A1 EP0654080A1 EP93916096A EP93916096A EP0654080A1 EP 0654080 A1 EP0654080 A1 EP 0654080A1 EP 93916096 A EP93916096 A EP 93916096A EP 93916096 A EP93916096 A EP 93916096A EP 0654080 A1 EP0654080 A1 EP 0654080A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- molecule
- peptide
- hiv
- sequence
- modified
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
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- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- -1 acetamidomethyl Chemical group 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910021502 aluminium hydroxide Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
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- 239000003729 cation exchange resin Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
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- 231100000433 cytotoxic Toxicity 0.000 description 1
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- 239000012153 distilled water Substances 0.000 description 1
- 108010078428 env Gene Products Proteins 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
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- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
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- 238000002523 gelfiltration Methods 0.000 description 1
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- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000000521 hyperimmunizing effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000002434 immunopotentiative effect Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 230000002637 immunotoxin Effects 0.000 description 1
- 239000002596 immunotoxin Substances 0.000 description 1
- 231100000608 immunotoxin Toxicity 0.000 description 1
- 229940051026 immunotoxin Drugs 0.000 description 1
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- 230000002458 infectious effect Effects 0.000 description 1
- 230000001524 infective effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 150000002614 leucines Chemical class 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 108010017391 lysylvaline Proteins 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 238000011587 new zealand white rabbit Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 229940092253 ovalbumin Drugs 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
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- 239000007787 solid Substances 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
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- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Substances CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 1
- QXTIBZLKQPJVII-UHFFFAOYSA-N triethylsilicon Chemical compound CC[Si](CC)CC QXTIBZLKQPJVII-UHFFFAOYSA-N 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 208000007089 vaccinia Diseases 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/16011—Human Immunodeficiency Virus, HIV
- C12N2740/16111—Human Immunodeficiency Virus, HIV concerning HIV env
- C12N2740/16122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
Definitions
- a live vaccine e.g. as part of the coat of a genetically modified virus such as polio or vaccinia.
- a further aspect of the invention thus provides a method for the prophylaxis or treatment of AIDS or related conditions, comprising administering an effective amount of a molecule in accordance with the invention.
- the invention provides a
- the peptide was analysed by HPLC after synthesis and found to be at least 98% pure and was therefore used, without further purification, for coupling to KLH for immunisation of rabbits.
- Figure 4 shows binding of sera from one rabbit (Pong) to cells infected with HIV-2.
- the cells were either
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Virology (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pressure Welding/Diffusion-Bonding (AREA)
Abstract
L'invention concerne une molécule comprenant un peptide possédant la séquence d'acides aminés lysine-proline-cystéine-valine-lysine-leucine-thréonine-proline-leucine-cystéine-valine (Séquence No.1), où chaque résidu de cystéine comporte une liaison bisulfure pontée à un autre résidu de cystéine ou est dérivé, de façon à simuler une partie d'une liaison bisulfure, ou bien des variantes fonctionnellement équivalentes dudit peptide imitant le comportement immunogène d'un déterminant antigénique de gp120 de la glycoprotéine enveloppe (env) de HIV. La séquence est extrêmement conservée, étant totalement conservée dans tous les isolats enregistrés de HIV-1 et HIV-2 et ne subit que des modifications peu importantes dans des isolats de SIV. Chaque résidu de cystéine contribuant à un pont bisulfure respectif (réel ou simulé par une dérivation appropriée), la molécule imite avec précision le comportement de la séquence correspondante de gp120 et choisit une réponse immune. De ce fait, on peut utiliser la molécule en tant que base d'un vaccin potentiel contre le SIDA et les états apparentés au SIDA, ainsi que dans le traitement du SIDA et des états apparentés.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB929215129A GB9215129D0 (en) | 1992-07-16 | 1992-07-16 | Development relating to human immunodeficiency viruses |
| GB9215129 | 1992-07-16 | ||
| PCT/GB1993/001503 WO1994002614A1 (fr) | 1992-07-16 | 1993-07-16 | PEPTIDES IMITANT LE DETERMINANT ANTIGENIQUE DE gp120 DE HIV |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP0654080A1 true EP0654080A1 (fr) | 1995-05-24 |
Family
ID=10718806
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP93916096A Withdrawn EP0654080A1 (fr) | 1992-07-16 | 1993-07-16 | PEPTIDES IMITANT LE DETERMINANT ANTIGENIQUE DE gp120 DE HIV |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP0654080A1 (fr) |
| JP (1) | JPH07509237A (fr) |
| AU (1) | AU681591B2 (fr) |
| CA (1) | CA2140151A1 (fr) |
| GB (1) | GB9215129D0 (fr) |
| WO (1) | WO1994002614A1 (fr) |
| ZA (1) | ZA935165B (fr) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4402756A1 (de) * | 1994-01-31 | 1995-08-03 | Boehringer Mannheim Gmbh | Spezifische Bindungssubstanzen für Antikörper und deren Verwendung für Immunoassays oder Vakzine |
| US6911527B1 (en) | 1999-01-11 | 2005-06-28 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | HIV related peptides |
| EP1159297A2 (fr) * | 1999-01-11 | 2001-12-05 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by the SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES | Nouveaux peptides associes au vih |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8714802D0 (en) * | 1987-06-24 | 1987-07-29 | Proteus Biotech Ltd | Synthetic polypeptides |
| FR2617944B1 (fr) * | 1987-07-06 | 1990-09-28 | Macc Sa | Perfectionnement aux chevalets |
| GB8828097D0 (en) * | 1988-12-01 | 1989-01-05 | Wellcome Found | Peptides |
| CA2035576A1 (fr) * | 1990-02-07 | 1991-08-08 | Alexander R. Neurath | Determinants antigeniques de forme de la glycoproteine gp 120 hiv-1 de l'enveloppe du virus l'immunodeficience humaine |
-
1992
- 1992-07-16 GB GB929215129A patent/GB9215129D0/en active Pending
-
1993
- 1993-07-16 CA CA002140151A patent/CA2140151A1/fr not_active Abandoned
- 1993-07-16 AU AU45788/93A patent/AU681591B2/en not_active Ceased
- 1993-07-16 JP JP6504265A patent/JPH07509237A/ja active Pending
- 1993-07-16 WO PCT/GB1993/001503 patent/WO1994002614A1/fr not_active Ceased
- 1993-07-16 ZA ZA935165A patent/ZA935165B/xx unknown
- 1993-07-16 EP EP93916096A patent/EP0654080A1/fr not_active Withdrawn
Non-Patent Citations (1)
| Title |
|---|
| See references of WO9402614A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2140151A1 (fr) | 1994-02-03 |
| AU681591B2 (en) | 1997-09-04 |
| JPH07509237A (ja) | 1995-10-12 |
| GB9215129D0 (en) | 1992-08-26 |
| AU4578893A (en) | 1994-02-14 |
| ZA935165B (en) | 1994-03-14 |
| WO1994002614A1 (fr) | 1994-02-03 |
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