CA2665186A1 - Stabilized therapeutic small helical antiviral peptides - Google Patents
Stabilized therapeutic small helical antiviral peptides Download PDFInfo
- Publication number
- CA2665186A1 CA2665186A1 CA002665186A CA2665186A CA2665186A1 CA 2665186 A1 CA2665186 A1 CA 2665186A1 CA 002665186 A CA002665186 A CA 002665186A CA 2665186 A CA2665186 A CA 2665186A CA 2665186 A1 CA2665186 A1 CA 2665186A1
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- Prior art keywords
- peptide
- amino acids
- capsid
- mammal
- containing virus
- 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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- 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
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- 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
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- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
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- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Virology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US84955106P | 2006-10-05 | 2006-10-05 | |
| US60/849,551 | 2006-10-05 | ||
| PCT/US2007/021156 WO2008045238A2 (en) | 2006-10-05 | 2007-10-02 | Stabilized therapeutic small helical antiviral peptides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2665186A1 true CA2665186A1 (en) | 2008-04-17 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002665186A Abandoned CA2665186A1 (en) | 2006-10-05 | 2007-10-02 | Stabilized therapeutic small helical antiviral peptides |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US8940864B2 (enExample) |
| EP (2) | EP2517720A1 (enExample) |
| JP (1) | JP2010505831A (enExample) |
| AU (1) | AU2007307254A1 (enExample) |
| CA (1) | CA2665186A1 (enExample) |
| ES (1) | ES2387827T3 (enExample) |
| WO (1) | WO2008045238A2 (enExample) |
| ZA (1) | ZA200901248B (enExample) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| JP2012503024A (ja) * | 2008-09-22 | 2012-02-02 | エルロン・セラピューティクス・インコーポレイテッド | ペプチド模倣大環状分子 |
| WO2010083347A2 (en) | 2009-01-14 | 2010-07-22 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| RU2582678C2 (ru) | 2010-08-13 | 2016-04-27 | Эйлерон Терапьютикс, Инк. | Пептидомиметические макроциклы |
| 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 |
| 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 |
| US11039620B2 (en) | 2014-02-19 | 2021-06-22 | Corning Incorporated | Antimicrobial glass compositions, glasses and polymeric articles incorporating the same |
| US9622483B2 (en) | 2014-02-19 | 2017-04-18 | Corning Incorporated | Antimicrobial glass compositions, glasses and polymeric articles incorporating the same |
| US11039621B2 (en) | 2014-02-19 | 2021-06-22 | Corning Incorporated | Antimicrobial glass compositions, glasses and polymeric articles incorporating the same |
| 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 |
| KR101972012B1 (ko) * | 2014-11-28 | 2019-04-24 | 서울대학교산학협력단 | 세포 투과성 스테이플 펩타이드, 이의 제조방법 및 그 용도 |
| US10253067B2 (en) | 2015-03-20 | 2019-04-09 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| US10059741B2 (en) | 2015-07-01 | 2018-08-28 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| WO2017018595A1 (ko) * | 2015-07-28 | 2017-02-02 | 동국대학교 산학협력단 | 이중 스테이플화된 펩타이드 및 이의 용도 |
| 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 |
| US11279734B2 (en) | 2017-12-01 | 2022-03-22 | Massachusetts Institute Of Technology | Solution-phase affinity selection of inhibitors from combinatorial peptide libraries |
| US20200102356A1 (en) * | 2018-10-01 | 2020-04-02 | NMC Inc. | Compositions and Methods for the Treatment of Huanglongbing (HLB) aka Citrus Greening in Citrus Plants |
| WO2022036049A2 (en) * | 2020-08-12 | 2022-02-17 | New York Blood Center, Inc. | Antiviral stapled peptides against sars-cov-2 |
Family Cites Families (16)
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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 |
| 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 |
| 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 |
| 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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| WO2008045238A2 (en) | 2008-04-17 |
| EP2073829A4 (en) | 2010-03-03 |
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