US5512667A
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Trifunctional intermediates for preparing 3'-tailed oligonucleotides
Assignee: DRUG ROYALTY TRUST 9
•
Filing: 1993-02-03
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Granted: 1996-04-30
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Expires: 2013-02-03
Abstract
Abstract Oligonucleotides having a low molecular weight tail molecules joined to the 3' terminus of the oligonucleotide via a linking molecule of the structure: Z is ##STR1## wherein ##STR2## m and m' are positive integers less than 11, n is 0 or 1 and Q is a connecting group, are synthesized by selectively reacting three independent functional groups on the linking molecule, i.e., an amine, a primary hydroxyl and a secondary hydroxyl, in a stepwise manner. A tail molecule R is first connected to the amino functionality of the linking molecule. Next the linking molecule-tail molecule combination is attached to a solid state support via the secondary hydroxyl group. The oligonucleotide is systematically stepwise synthesized beginning on the primary hydroxyl group followed by release of the oligonucleotide having the low molecular weight tailed joined to its 3' terminus from the solid state support.
Inventors
- 👤 Michael W. Reed
- 👤 Rich B. Meyer, Jr.
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-05 03:11
CPC Classifications
C; C07; C07D; C07D401/00; C07D401/02; C07D401/06; C07D207/00; C07D207/02; C07D207/04; C07D207/10; C07D207/12; C07H; C07H21/00
Claims Analysis
Total Claims: 19
Claim 1
Independent Claim
80 words
A compound having the formula shown below: "wherein ODN represents an oligonucleotide whose terminal 3'-oxygen is attached to the above phosphate moiety" wherein Z is selected from a group consisting of ##STR22## n is 0 or 1, Q is a connecting group selected from a group consisting of alkyl, alkoxy, alkoxyalkyl, alkenyl, cycloalkyl, aryl, aryloxy, aralkyl, heterocyclic, heteroaryl, substituted aryl and substituted aralkyl; and R is selected from the group consisting of intercalating groups, cleaving groups, cholesterol and lipophilic groups.
Claim 2
Dependent Claim
80 words
A compound having the formula shown below: "wherein ODN represents an oligonucleotide whose terminal 3'-oxygen is attached to the above phosphate moiety" wherein Z is selected from a group consisting of ##STR22## n is 0 or 1, Q is a connecting group selected from a group consisting of alkyl, alkoxy, alkoxyalkyl, alkenyl, cycloalkyl, aryl, aryloxy, aralkyl, heterocyclic, heteroaryl, substituted aryl and substituted aralkyl; and R is selected from the group consisting of intercalating groups, cleaving groups, cholesterol and lipophilic groups.
Claim 3
Dependent Claim
38 words
A compound of claim 1 wherein: said R group is selected from a group consisting of cholesterol, acridine, ellipticine, methidium, ethidium, phenanthroline, 2-hydroxyethanethiolato-2,2', 2"-terpyridine-platinum(II), quinoxaline, an EDTA ligand for attaching Fe and a phenanthroline ligand for attaching Cu.
Claim 4
Dependent Claim
16 words
A compound of claim 1 wherein Z is ##STR23## n is 0; and R is cholesterol.
Claim 5
Dependent Claim
16 words
A compound of claim 1 wherein Z is ##STR24## n is 0; and R is 9-acridine.
Claim 6
Dependent Claim
87 words
A compound having the structure: ##STR25## wherein Z is selected from a group consisting of ##STR26## m and m' independently are positive integers less than 11; n is 0 or 1; Q is a connecting group selected from a group consisting of alkyl, alkoxy, alkoxyalkyl, alkenyl, cycloalkyl, aryl, aryloxy, aralkyl, heterocyclic, heteroaryl, substituted aryl and substituted aralkyl; R is selected from the group consisting of reporter groups, intercalating groups, cleaving groups, cholesterol and lipophilic groups; Y is H or dimethoxytrityl; and X is a solid phase support.
Claim 7
Dependent Claim
87 words
A compound having the structure: ##STR25## wherein Z is selected from a group consisting of ##STR26## m and m' independently are positive integers less than 11; n is 0 or 1; Q is a connecting group selected from a group consisting of alkyl, alkoxy, alkoxyalkyl, alkenyl, cycloalkyl, aryl, aryloxy, aralkyl, heterocyclic, heteroaryl, substituted aryl and substituted aralkyl; R is selected from the group consisting of reporter groups, intercalating groups, cleaving groups, cholesterol and lipophilic groups; Y is H or dimethoxytrityl; and X is a solid phase support.
Claim 8
Dependent Claim
72 words
A compound of claim, 5 wherein R is selected from the group consisting of cholesterol, biotin, acridine, fluorescein, rhodamine, Lissamine rhodamine B, Malachite Green, erythrosin, tetramethylrhodamine, eosin, pyrene, anthracene, 4-dimethylaminonapthalene, 2-dimethylaminonaphthalene, 7-dimethylamino-4-methylcoumarin, 7-dimethylaminocoumarin, 7-hydroxy-4-methylcoumarin, 7-hydroxycoumarin, 7-methoxycoumarin, 7-acetoxycoumarin, 7-diethylamino-3-phenyl-4-methylcoumarin, isoluminol, benzophenone, dansyl, dabsyl, mansyl, sulforhodamine, 4-acetamido-4-stilbene-2,2'-disulfonic acid disodium salt, 4-benzamido-4'-stilbene-2,2'-disulfonic acid disodium salt, ellipticine, methidium, ethydium, phenanthroline, 2-hydroxyethanethiolato-2,2', 2"-terpyridine-platinium-(II), quinoxaline, an EDTA ligand for attaching Fe and a phenanthroline ligand for attaching Cu.
Claim 9
Dependent Claim
17 words
A compound of claim 5 wherein X is a controlled pore glass support derivatized with an alkylamine.
Claim 10
Dependent Claim
9 words
A compound of claim 5 wherein Y is H.
Claim 11
Dependent Claim
9 words
A compound of claim 5 of the structure: ##STR27##
Claim 12
Dependent Claim
9 words
A compound of claim 9 wherein n is 1.
Claim 13
Dependent Claim
83 words
A compound of the structure: ##STR28## wherein Z is selected from a group consisting of ##STR29## m and m' independently are positive integers less than 11; n is 0 or 1; Q is a connecting group selected from a group consisting of alkyl, alkoxy, alkoxyalkyl, alkenyl, cycloalkyl, aryl, aryloxy, aralkyl, heterocyclic, heteroaryl, substituted aryl and substituted aralkyl; R is selected from the group consisting of reporter groups, intercalating groups, cleaving groups, cholesterol and phospholipids; X is hydrogen, and Y is H or dimethoxytrityl.
Claim 14
Dependent Claim
83 words
A compound of the structure: ##STR28## wherein Z is selected from a group consisting of ##STR29## m and m' independently are positive integers less than 11; n is 0 or 1; Q is a connecting group selected from a group consisting of alkyl, alkoxy, alkoxyalkyl, alkenyl, cycloalkyl, aryl, aryloxy, aralkyl, heterocyclic, heteroaryl, substituted aryl and substituted aralkyl; R is selected from the group consisting of reporter groups, intercalating groups, cleaving groups, cholesterol and phospholipids; X is hydrogen, and Y is H or dimethoxytrityl.
Claim 15
Dependent Claim
72 words
A compound of claim 11 wherein R is selected from the group consisting of cholesterol, biotine, acridine, fluorescein, rhodamine, Lissamine rhodamine B, Malachite Green, erythrosin, tetramethylrhodamine, eosin, pyrene, anthracene, 4-dimethylaminonapthalene, 2-dimethylaminonaphthalene, 7-dimethylamino-4-methylcoumarin, 7-dimethylaminocoumarin, 7-hydroxy-4-methylcoumarin, 7-hydroxycoumarin, 7-methoxycoumarin, 7-acetoxycoumarin, 7-diethylamino-3-phenyl-4-methylcoumarin, isoluminol, benzophenone, dansyl, dabsyl, mansyl, sulforhodamine, 4-acetamido-4-stilbene-2,2'-disulfonic acid disodium salt, 4-benzamido-4'-stilbene-2,2'-disulfonic acid disodium salt, ellipticine, methidium, ethydium, phenanthroline, 2-hydroxyethanethiolato-2,2', 2"-terpyridine-platinium-(II), quinoxaline, an EDTA ligand for attaching Fe and a phenanthroline ligand for attaching Cu.
Claim 16
Dependent Claim
10 words
A compound of claim 11 which has the structure: ##STR30##
Claim 17
Dependent Claim
9 words
A compound of claim 13 wherein Y is H.
Claim 18
Dependent Claim
13 words
A compound of claim 13 wherein n is O; and R is cholesterol.
Claim 19
Dependent Claim
16 words
A compound of claim 13 wherein n is 1; Q is ethyl; and R is 9-acridine.
References Cited (Backward Citations)
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1999-04-30 | 1999-10-30 | 2000-04-30 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2003-04-30 | 2003-10-30 | 2004-04-30 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2007-04-30 | 2007-10-30 | 2008-04-30 | $7700.00 | Window Closed / Lapsed |