Covalently linked oligonucleotide minor grove binder conjugates

• US 6,084,102 A
• Filed: 08/27/1998
• Issued: 07/04/2000
• Est. Priority Date: 04/03/1995
• Status: Expired due to Term

• Current Assignee: Epoch Pharmaceuticals, Inc.
• Original Assignee: Epoch Pharmaceuticals, Inc.
• Inventors: Meyer, Rich B. Jr., Lukhtanov, Eugeny A., Kutyavin, Igor V., Gamper, Howard B.
• Primary Examiner(s): Riley, Jezia
• Application Number:
  US09/141,764
• Time in Patent Office: 677 Days
• Field of Search: 514/44, 514/183, 514/419, 536/25.3, 536/25.32, 546/270.1, 546/271.1, 548/311.1, 548/312.4, 548/100
• US Class Current: 548/100
• CPC Class Codes: C07D 207/34 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: C07H 19/073 with 2-deoxyribosyl as the saccharide radical
• CPC Class Codes: C07H 19/173 with 2-deoxyribosyl as the saccharide radical
• CPC Class Codes: C07H 19/23 Heterocyclic radicals containing two or more heterocyclic rings condensed among themselves or condensed with a common carbocyclic ring system, not provided for in groups C07H19/14 - C07H19/22
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C07H 21/04 with deoxyribosyl as saccharide radical
• CPC Class Codes: C12Q 1/6813 Hybridisation assays
• CPC Class Codes: C12Q 2525/197 incorporating a spacer/coupling moiety
• CPC Class Codes: C12Q 2527/107 Temperature of melting, i.e. Tm

Abstract

Minor groove binding molecules are covalently bound to oligonucleotides which in their base sequence are complementary to a target sequence of single stranded or double stranded DNA, RNA or hybrids thereof. The covalently bound oligonucleotide minor groove binder conjugates strongly bind to the target sequence of the complementary strand.

Claims

1. A compound of the formula ##STR19## where R is CONH₂ or t-butyloxy-carbonyl, and R₁ is 2,3,5,6-tetrafluorophenyloxy.

2. A compound in accordance with claim 1 where R is CONH₂.

3. A compound in accordance with claim 1 where R is t-butyloxycarbonyl.

4. A compound of the formula ##STR20## where R is CONH₂ or t-butyloxycarbonyl, and R₁ is 2,3,5,6-tetrafluorophenyloxy.

5. A compound in accordance with claim 4 where R is CONH₂.

6. A compound in accordance with claim 4 where R is t-butyloxycarbonyl.

7. A compound of the formula ##STR21## where R₁ is 2,3,5,6-tetrafluorophenyloxy.

8. A compound of the formula ##STR22## where CPG represent a solid phase support, and

Tr represents a triphenylmethyl or substituted triphenylmethyl group.

9. A compound in accordance with claim 8 where Tr represents a dimethoxytriphenylmethyl group.

10. A compound of the formula ##STR23## where n is an integer from 1 and 5;

R₁ is H, t-butyloxycarbonyl or tBoc-NH(CH₂)₆ CO where tBoc represent t-butyloxycarbonyl.

11. A compound in accordance with claim 10 where n is 1.

12. A compound in accordance with claim 10 where n is 5.

13. A compound in accordance with claim 10 where R₁ is t-butyloxy-carbonyl.

14. A compound in accordance with claim 10 where R₁ is H.

15. A compound in accordance with claim 10 where R₁ is t-Boc-NH(CH₂)₆ CO--.

16. A compound in accordance with claim 12 where R₁ is H.

17. A compound in accordance with claim 12 where R₁ is tBOC-NH(CH₂)₆ CO.