WO1998004575A3 - Lipophilic oligonucleotide analogs - Google Patents
Lipophilic oligonucleotide analogs Download PDFInfo
- Publication number
- WO1998004575A3 WO1998004575A3 PCT/US1996/012530 US9612530W WO9804575A3 WO 1998004575 A3 WO1998004575 A3 WO 1998004575A3 US 9612530 W US9612530 W US 9612530W WO 9804575 A3 WO9804575 A3 WO 9804575A3
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- lipophilic
- oligonucleotide analogs
- contain
- oligonucleotides
- substitutions
- Prior art date
Links
- 108091034117 Oligonucleotide Proteins 0.000 title abstract 5
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 abstract 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 abstract 2
- 238000006467 substitution reaction Methods 0.000 abstract 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract 2
- 210000004027 cell Anatomy 0.000 abstract 1
- 210000000170 cell membrane Anatomy 0.000 abstract 1
- 238000009792 diffusion process Methods 0.000 abstract 1
- 125000003729 nucleotide group Chemical group 0.000 abstract 1
- 238000005192 partition Methods 0.000 abstract 1
- 235000000346 sugar Nutrition 0.000 abstract 1
- 150000008163 sugars Chemical class 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention discloses lipophilic oligonucleotide analogs that are capable of efficient passive diffusion across cell membranes. These oligonucleotides contain at least two nucleotide residues and have an octanol:water partition coefficient of about -0.3 to + 2.5 and a solubility in water of at least 0.001 νg/mL. Invention embodiments which include lipophilic oligonucleotide analogs having either at least 60 % of the internucleotide linkages are lipophilic, or at least 60 % of the bases contain lipophilic substitutions, or at least 60 % of the sugars contain lipophilic substitutions, or a combination of these sums to 60 %. These oligonucleotides may be conjugated to a label and used to visualize cells or subcellular compartments.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US1996/012530 WO1998004575A2 (en) | 1996-07-31 | 1996-07-31 | Lipophilic oligonucleotide analogs |
| EP96926831A EP0923596A2 (en) | 1996-07-31 | 1996-07-31 | Lipophilic oligonucleotide analogs |
| CA002261704A CA2261704A1 (en) | 1996-07-31 | 1996-07-31 | Lipophilic oligonucleotide analogs |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US1996/012530 WO1998004575A2 (en) | 1996-07-31 | 1996-07-31 | Lipophilic oligonucleotide analogs |
| CA002261704A CA2261704A1 (en) | 1996-07-31 | 1996-07-31 | Lipophilic oligonucleotide analogs |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO1998004575A2 WO1998004575A2 (en) | 1998-02-05 |
| WO1998004575A3 true WO1998004575A3 (en) | 1998-03-19 |
Family
ID=25680807
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1996/012530 WO1998004575A2 (en) | 1996-07-31 | 1996-07-31 | Lipophilic oligonucleotide analogs |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP0923596A2 (en) |
| CA (1) | CA2261704A1 (en) |
| WO (1) | WO1998004575A2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7575918B2 (en) | 1999-04-14 | 2009-08-18 | The Penn State Research Foundation | Tissue-specific and pathogen-specific ribozymes |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005537028A (en) | 2002-06-26 | 2005-12-08 | ザ ペン ステート リサーチ ファウンデーション | Methods and materials for treating human papillomavirus infections |
| MX2011008563A (en) | 2009-02-13 | 2012-06-19 | Chem Inc X | Methods of creating and screening dna-encoded libraries. |
| EP3000898B1 (en) | 2013-05-21 | 2020-11-18 | Hitgen Inc. | Drug target capturing method |
| CA3127137A1 (en) | 2019-01-22 | 2020-07-30 | Vipergen Aps | A method for screening of an in vitro display library within a cell |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4904582A (en) * | 1987-06-11 | 1990-02-27 | Synthetic Genetics | Novel amphiphilic nucleic acid conjugates |
| WO1990010448A2 (en) * | 1989-03-07 | 1990-09-20 | Genentech, Inc. | Covalent conjugates of lipid and oligonucleotide |
| WO1993010820A1 (en) * | 1991-11-26 | 1993-06-10 | Gilead Sciences, Inc. | Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines |
| EP0547008A1 (en) * | 1991-11-26 | 1993-06-16 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. | New antisense oligonucleotides |
| US5420330A (en) * | 1990-09-07 | 1995-05-30 | Pharmacia P-L Biochemicals Inc. | Lipo-phosphoramidites |
| WO1996029337A1 (en) * | 1995-03-23 | 1996-09-26 | Hybridon, Inc. | Thiono triester modified antisense oligodeoxynucleotide phosphorothioates |
| US5633360A (en) * | 1992-04-14 | 1997-05-27 | Gilead Sciences, Inc. | Oligonucleotide analogs capable of passive cell membrane permeation |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5484908A (en) | 1991-11-26 | 1996-01-16 | Gilead Sciences, Inc. | Oligonucleotides containing 5-propynyl pyrimidines |
-
1996
- 1996-07-31 EP EP96926831A patent/EP0923596A2/en not_active Withdrawn
- 1996-07-31 CA CA002261704A patent/CA2261704A1/en not_active Abandoned
- 1996-07-31 WO PCT/US1996/012530 patent/WO1998004575A2/en active Application Filing
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4904582A (en) * | 1987-06-11 | 1990-02-27 | Synthetic Genetics | Novel amphiphilic nucleic acid conjugates |
| WO1990010448A2 (en) * | 1989-03-07 | 1990-09-20 | Genentech, Inc. | Covalent conjugates of lipid and oligonucleotide |
| US5420330A (en) * | 1990-09-07 | 1995-05-30 | Pharmacia P-L Biochemicals Inc. | Lipo-phosphoramidites |
| WO1993010820A1 (en) * | 1991-11-26 | 1993-06-10 | Gilead Sciences, Inc. | Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines |
| EP0547008A1 (en) * | 1991-11-26 | 1993-06-16 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. | New antisense oligonucleotides |
| US5633360A (en) * | 1992-04-14 | 1997-05-27 | Gilead Sciences, Inc. | Oligonucleotide analogs capable of passive cell membrane permeation |
| WO1996029337A1 (en) * | 1995-03-23 | 1996-09-26 | Hybridon, Inc. | Thiono triester modified antisense oligodeoxynucleotide phosphorothioates |
Non-Patent Citations (4)
| Title |
|---|
| J.F.HUGHES ET AL.: "Lipid Membrane Permeability of 2'-Modified Derivatives of Phosphorothioate Oligonucleotides.", JOURNAL OF PHARMACEUTICAL SCIENCES, vol. 83, no. 4, April 1994 (1994-04-01), pages 597 - 600, XP002052615 * |
| J.M.DAGLE ET AL.: "Physical Properties of Oligonucleotides Containing Phosphoramidate-Modified Internucleoside Linkages.", NUCLEIC ACIDS RESEARCH., vol. 19, no. 8, 1991, OXFORD GB, pages 1805 - 1810, XP002052616 * |
| S.AKHTAR ET AL.: "Interactions of Antisense DNA Oligonucleotide Analogs with Phospholipid Membranes (Liposomes).", NUCLEIC ACIDS RESEARCH., vol. 19, no. 20, 1991, OXFORD GB, pages 5551 - 5559, XP002052617 * |
| Z.ZHANG ET AL.: "Thiono Triester Modified Antisense Oligonucleotides for Inhibition of Human Cytomegalovirus in vitro.", BIOORGANIC AND MEDICINAL CHEMISTRY LETTERS, vol. 6, no. 16, August 1996 (1996-08-01), pages 1911 - 1916, XP000677176 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7575918B2 (en) | 1999-04-14 | 2009-08-18 | The Penn State Research Foundation | Tissue-specific and pathogen-specific ribozymes |
Also Published As
| Publication number | Publication date |
|---|---|
| EP0923596A2 (en) | 1999-06-23 |
| CA2261704A1 (en) | 1998-02-05 |
| WO1998004575A2 (en) | 1998-02-05 |
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