Boronic acid-containing polynucleotides

• US 5,831,045 A
• Filed: 04/11/1997
• Issued: 11/03/1998
• Est. Priority Date: 08/05/1996
• Status: Expired due to Fees

• Current Assignee: Porlinx Incorporated
• Original Assignee: Porlinx Incorporated
• Inventors: Stolowitz, Mark L., Kaiser, Robert J.
• Primary Examiner(s): Marschel, Ardin H.
• Assistant Examiner(s): Riley, Jezia
• Application Number:
  US08/834,001
• Time in Patent Office: 571 Days
• Field of Search: 435/6, 536/22.1, 536/24.3, 536/27.1, 536/27.11, 536/27.13
• 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 modified polynucleotide having the formula:

##STR23## wherein z is an integer of from 1 to 1000;

each R¹¹ is independently selected from the group consisting of --H and --OH;

R¹² and R¹³ are each members independently selected from the group consisting of hydroxyl, protected hydroxyl, monophosphate ester, diphosphate ester and triphosphate ester;

each P¹ and P² is independently selected from the group consisting of --P(O)(OH)--, --P(O)(NH₂)--, --P(S)(OH)--, --P(O)(CH₃)--, and pharmaceutically acceptable salts thereof;

each Nu¹¹, Nu¹² and Nu¹³ is independently selected from the group consisting of ##STR24## adenine, guanine, thymine and cytosine, 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;

with the proviso that at least one and no more than thirty of Nu¹¹, Nu¹² and Nu¹³ are other than adenine, guanine, thymine or cytosine.

2. A modified polynucleotide in accordance with claim 1, wherein R¹² is hydroxyl and R¹³ is a monophosphate ester.

3. A modified polynucleotide in accordance with claim 1, wherein z is an integer of from about 5 to about 100.

4. A modified polynucleotide in accordance with claim 1, wherein z is an integer of from about 10 to about 30.

5. A modified polynucleotide in accordance with claim 1, wherein one of Nu¹¹, Nu¹² or Nu¹³ is a member selected from the group consisting of ##STR25## wherein --X-- and --(Y)_p taken together comprise a radical selected from the group consisting of ##STR26## in which X¹ is a linking group fragment comprising of from 3 to 23 carbon atoms.