CA2725227A1 - Antiviral cell penetrating peptides - Google Patents
Antiviral cell penetrating peptides Download PDFInfo
- Publication number
- CA2725227A1 CA2725227A1 CA2725227A CA2725227A CA2725227A1 CA 2725227 A1 CA2725227 A1 CA 2725227A1 CA 2725227 A CA2725227 A CA 2725227A CA 2725227 A CA2725227 A CA 2725227A CA 2725227 A1 CA2725227 A1 CA 2725227A1
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- Prior art keywords
- amino acids
- peptide
- seq
- nyad
- mammal
- 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.)
- Abandoned
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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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C12N2740/16211—Human Immunodeficiency Virus, HIV concerning HIV gagpol
- C12N2740/16222—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Virology (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US5095508P | 2008-05-06 | 2008-05-06 | |
| US61/050,955 | 2008-05-06 | ||
| PCT/US2009/042913 WO2009137532A1 (en) | 2008-05-06 | 2009-05-05 | Antiviral cell penetrating peptides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2725227A1 true CA2725227A1 (en) | 2009-11-12 |
Family
ID=40957984
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2725227A Abandoned CA2725227A1 (en) | 2008-05-06 | 2009-05-05 | Antiviral cell penetrating peptides |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US8324153B2 (enExample) |
| EP (1) | EP2283033A1 (enExample) |
| JP (1) | JP2011522796A (enExample) |
| AU (1) | AU2009244400B2 (enExample) |
| CA (1) | CA2725227A1 (enExample) |
| WO (1) | WO2009137532A1 (enExample) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008045238A2 (en) * | 2006-10-05 | 2008-04-17 | New York Blood Center, Inc. | Stabilized therapeutic small helical antiviral peptides |
| US8937154B2 (en) | 2006-10-05 | 2015-01-20 | New York Blood Center, Inc. | Stabilized therapeutic small helical antiviral peptides |
| US8889632B2 (en) | 2007-01-31 | 2014-11-18 | Dana-Farber Cancer Institute, Inc. | Stabilized p53 peptides and uses thereof |
| CA2682174C (en) | 2007-03-28 | 2021-04-06 | President And Fellows Of Harvard College | Stitched polypeptides |
| AU2009244400B2 (en) * | 2008-05-06 | 2012-12-20 | New York Blood Center | Antiviral cell penetrating peptides |
| RU2582678C2 (ru) | 2010-08-13 | 2016-04-27 | Эйлерон Терапьютикс, Инк. | Пептидомиметические макроциклы |
| WO2012137036A1 (en) * | 2011-04-04 | 2012-10-11 | Centre National De La Recherche Scientifique | Cell penetrating peptides for intracellular delivery of molecules |
| CA2834657A1 (en) * | 2011-04-29 | 2012-11-01 | Kinemed, Inc. | Chemical modification of apolipoprotein mimetic peptides for the production of therapeutic agents |
| RU2639523C2 (ru) | 2011-10-18 | 2017-12-21 | Эйлерон Терапьютикс, Инк. | Пептидомиметические макроциклы и их применение |
| WO2013123266A1 (en) | 2012-02-15 | 2013-08-22 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| EP2819688A4 (en) | 2012-02-15 | 2015-10-28 | Aileron Therapeutics Inc | PEPTIDOMIMETIC MACROCYCLES CROSS-LINKED WITH TRIAZOLE AND THIOETHER |
| WO2014053880A1 (en) | 2012-10-04 | 2014-04-10 | Centre National De La Recherche Scientifique | Cell penetrating peptides for intracellular delivery of molecules |
| CN104812384B (zh) | 2012-11-01 | 2020-09-18 | 爱勒让治疗公司 | 二取代的氨基酸及其制备和使用方法 |
| BR112017005598A2 (pt) | 2014-09-24 | 2017-12-12 | Aileron Therapeutics Inc | macrociclos peptidomiméticos e usos dos mesmos |
| SG10201902598VA (en) | 2014-09-24 | 2019-04-29 | Aileron Therapeutics Inc | Peptidomimetic macrocycles and formulations thereof |
| CN105622732B (zh) * | 2014-10-30 | 2019-10-25 | 中国科学院武汉病毒研究所 | 猴病毒40衣壳蛋白vp1在作为细胞穿膜蛋白中的应用 |
| PL3237436T3 (pl) | 2014-12-24 | 2020-03-31 | Aadigen, Llc | Peptydy i nanocząsteczki do wewnątrzkomórkowego dostarczania cząsteczek |
| US10253067B2 (en) | 2015-03-20 | 2019-04-09 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| CN108368161A (zh) | 2015-09-10 | 2018-08-03 | 艾瑞朗医疗公司 | 作为mcl-1调节剂的拟肽大环化合物 |
| US20200354413A1 (en) | 2017-12-15 | 2020-11-12 | Dana-Farber Cancer Institute, Inc. | Stabilized peptide-mediated targeted protein degradation |
| CA3089279A1 (en) | 2018-02-07 | 2019-08-15 | Dana-Farber Cancer Institute, Inc. | Cell-permeable stapled peptide modules for cellular delivery |
| EP3980048A4 (en) * | 2019-06-07 | 2023-11-29 | The Curators Of The University Of Missouri | PEPTIDE INHIBITORS FOR HIV CAPSID INHIBITION |
| CA3173973A1 (en) * | 2020-03-04 | 2021-09-10 | Dana-Farber Cancer Institute, Inc. | Antiviral structurally-stabilized sars-cov-2 peptides and uses thereof |
Family Cites Families (20)
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| US6187548B1 (en) | 1993-05-23 | 2001-02-13 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Methods using human calcium sensor protein, fragments thereof and DNA encoding same |
| US6239270B1 (en) | 1993-05-24 | 2001-05-29 | Rhone-Poulenc Rorer S.A. | Nucleic acids encoding human calcium sensor protein |
| JP3534417B2 (ja) * | 1997-03-10 | 2004-06-07 | ロシュ ダイアグノスティックス ゲーエムベーハー | Ｈｉｖ抗原及びｈｉｖ抗体の同時決定方法 |
| US6790950B2 (en) | 1999-04-09 | 2004-09-14 | Pharmacia & Upjohn Company | Anti-bacterial vaccine compositions |
| ES2439645T3 (es) | 1999-04-09 | 2014-01-24 | Zoetis P&U Llc | Bacteria pasteurelácea atenuada que tiene una mutación en un gen de virulencia |
| US7192713B1 (en) * | 1999-05-18 | 2007-03-20 | President And Fellows Of Harvard College | Stabilized compounds having secondary structure motifs |
| AUPQ776100A0 (en) | 2000-05-26 | 2000-06-15 | Australian National University, The | Synthetic molecules and uses therefor |
| US6653102B2 (en) | 2000-10-17 | 2003-11-25 | Myriad Genetics, Inc. | Nucleic acid encoding a phosphatase 2C that interacts with Fe 65 |
| EP1680443B9 (en) * | 2003-11-05 | 2014-09-03 | Dana-Farber Cancer Institute, Inc. | Stabilized alpha helical peptides and uses thereof |
| WO2008008998A2 (en) | 2006-07-13 | 2008-01-17 | Cell Signaling Technology, Inc. | Reagents for the detection of protein phosphorylation in signaling pathways |
| US20100159477A1 (en) | 2006-07-13 | 2010-06-24 | Peter Hornbeck | Reagents for the detection of protein phosphorylation in signaling pathways |
| KR20090059148A (ko) | 2006-09-11 | 2009-06-10 | 더 보드 오브 트러스티즈 오브 더 유니버시티 오브 일리노이 | 쿠프레독신 유래된 펩티드의 변형 및 이의 이용 방법 |
| WO2008045238A2 (en) | 2006-10-05 | 2008-04-17 | New York Blood Center, Inc. | Stabilized therapeutic small helical antiviral peptides |
| US8937154B2 (en) | 2006-10-05 | 2015-01-20 | New York Blood Center, Inc. | Stabilized therapeutic small helical antiviral peptides |
| US8889632B2 (en) | 2007-01-31 | 2014-11-18 | Dana-Farber Cancer Institute, Inc. | Stabilized p53 peptides and uses thereof |
| JP5078401B2 (ja) * | 2007-03-27 | 2012-11-21 | 株式会社Ａｄｅｋａ | 防水シート |
| CA2700925C (en) * | 2007-09-26 | 2016-08-23 | Dana Farber Cancer Institute | Methods and compositions for modulating bcl-2 family polypeptides |
| EP2247606B1 (en) * | 2008-01-23 | 2019-08-21 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for the treatment of viral infections |
| AU2009244400B2 (en) * | 2008-05-06 | 2012-12-20 | New York Blood Center | Antiviral cell penetrating peptides |
| EP3401684B1 (en) * | 2008-10-10 | 2022-03-16 | Dana Farber Cancer Institute, Inc. | Chemical modulators of pro-apoptotic bax and bcl-2 polypeptides |
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| AU2009244400B2 (en) | 2012-12-20 |
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| US20090281041A1 (en) | 2009-11-12 |
| WO2009137532A1 (en) | 2009-11-12 |
| US8324153B2 (en) | 2012-12-04 |
| AU2009244400A2 (en) | 2010-11-11 |
| US8933019B2 (en) | 2015-01-13 |
| JP2011522796A (ja) | 2011-08-04 |
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