Boronic acid-contaning nucleic acid monomers

• US 5,831,046 A
• Filed: 08/05/1996
• Issued: 11/03/1998
• Est. Priority Date: 08/05/1996
• Status: Expired due to Fees

• Current Assignee: Prolinx, Inc.
• Original Assignee: Prolinx, Inc.
• Inventors: Stolowitz, Mark L., Kaiser, Robert J.
• Primary Examiner(s): Marschel, Ardin H.
• Assistant Examiner(s): Riley, Jezia
• Application Number:
  US08/692,429
• Time in Patent Office: 820 Days
• Field of Search: 435/6, 536/22.1, 536/23.1, 536/24.3, 536/25.3, 546/1, 546/20, 548/517, 548/518
• US Class Current: 536/22.1
• 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 23/00 Compounds containing boron, silicon, or a metal, e.g. chelates, vitamin B12 esters with inorganic acids C07H11/00; metal salts, see parent compounds
• CPC Class Codes: C12P 19/34 Polynucleotides, e.g. nucleic acids, oligoribonucleotides

Abstract

Modified nucleotides and polynucleotides which are useful in hybridization assays for the detection of target genes are provided. The modified polynucleotides contain at least one boronic acid moiety which is attached to a nucleotide base in a position which does not interfere with the hydrogen bonding capabilities of that base during duplex formation. The modified polynucleotides are typically formed from naturally occurring nucleotides and one or more modified nucleotides.

Claims

1. A compound having the formula:

##STR23## wherein R¹, R² and R³ are each members independently selected from the group consisting of hydrogen, hydroxyl, protected hydroxyl, monophosphate ester, diphosphate ester, and triphosphate ester;

Nu is a radical selected from the group consisting of ##STR24## wherein X is a linking group comprising of from 7 to 30 carbon atoms, a portion of which is an aromatic ring; and

Y is a member selected from the group consisting of --B(OH)₂, --B(OH)(OR) and --B(OR)(OR'"'"'), wherein R and R'"'"' are each independently lower alkyl groups having from one to six carbon atoms; and

p is an integer of from 1 to 3.

2. A compound in accordance with claim 1, wherein Y is --B(OH)₂.

3. A compound having the formula:

##STR25## wherein R¹, R² and R³ are each members independently selected from the group consisting of hydrogen, hydroxyl, protected hydroxyl, monophosphate ester, diphosphate ester, and triphosphate ester;

Nu is a radical selected from the group consisting of ##STR26## wherein p is an integer of from 1 to 3, and --X-- and --(Y)_p taken together comprise a radical selected from the group consisting of ##STR27## in which X¹ is a linking group fragment comprising of from 3 to 23 carbon atoms.

5. A compound in accordance with claim 3, wherein --X-- and --(Y)_p taken together comprise a radical selected from the group consisting of ##STR30## in which X¹ is a linking group fragment comprising of from 3 to 23 carbon atoms.

4. A compound having the formula:

##STR28## wherein R¹, R² and R³ are each members independently selected from the group consisting of hydrogen, hydroxyl, protected hydroxyl, monophosphate ester, diphosphate ester, and triphosphate ester;

Nu is a radical selected from the group consisting of ##STR29## wherein X is a linking group comprising of from 7 to 30 carbon atoms, a portion of which is an aromatic ring, and further comprising a diradical --CH═

CH-- attached directly to the heterocyclic portion of said Nu; and

Y is a member selected from the group consisting of --B(OH)₂, --B(OH)(OR) and --B(OR)(OR'"'"'), wherein R and R'"'"' are each independently lower alkyl groups having from one to six carbon atoms; and

p is an integer of from 1 to 3.

6. A compound in accordance with claim 4, wherein X is a member selected from the group consisting of --CH═

CH--CH₂ --NHCOAr--, --CH═

CH--CH₂ --NHAr--, --CH═

CH--CH₂ --O--Ar--, --CH═

CH--CONH--Ar--, --CH═

CH--CH₂ --CONH--Ar--, --CH═

CH--CH₂ --NHCO--(CH₂)_n --NHCO--Ar--, and --CH═

CH--CH₂ --NHCO--(CH₂)_n --NHCO--(CH₂)_m --CONH--Ar-- wherein Ar represents a divalent aromatic ring selected from the group consisting of phenyl and naphthyl and n and m independently represent integers of from 1 to 6.

7. A compound in accordance with claim 4, wherein X is ##STR31## wherein n and m independently represent integers of from 1 to 6, Y is --B(OH)₂ and p is 1 or 2.

8. A compound in accordance with claim 4 having the formula:

##STR32##