Peptide nucleic acids having amino acid side chains

• US 5,719,262 A
• Filed: 07/24/1996
• Issued: 02/17/1998
• Est. Priority Date: 11/22/1993
• Status: Expired due to Term

• Current Assignee: Deceased, Ole Buchardt, Dorte Buchardt, Michael Egholm, Peter E. Nielsen, Rolf H. Berg
• Original Assignee: Deceased, Ole Buchardt, Dorte Buchardt, Michael Egholm, Peter E. Nielsen, Rolf H. Berg
• Inventors: Buchardt, legal representative, by Dorte, Egholm, Michael, Nielsen, Peter Eigil, Berg, Rolf Henrik, Buchardt, deceased, Ole
• Primary Examiner(s): Marschel, Ardin H.
• Application Number:
  US08/685,484
• Time in Patent Office: 573 Days
• Field of Search: 435/6, 435/810, 436/501, 530/300, 530/350, 528/310, 536/23.1, 536/24.1, 536/24.3-24.33, 935/77, 935/78
• US Class Current: 530/300
• 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: C07K 14/003 Peptide-nucleic acids (PNAs)
• CPC Class Codes: C07K 5/06139 with the first amino acid being heterocyclic
• CPC Class Codes: C12Q 1/68 involving nucleic acids
• CPC Class Codes: C12Q 1/6869 Methods for sequencing
• CPC Class Codes: C12Q 2535/107 Maxam and Gilbert method, i.e. sequential release and detection of nucleotides

Abstract

A novel class of compounds, known as peptide nucleic acids, bind complementary DNA and RNA strands more strongly than the corresponding DNA or RNA strands, and exhibit increased sequence specificity and solubility. The peptide nucleic acids comprise ligands selected from a group consisting of naturally-occurring nucleobases and non-naturally-occurring nucleobases attached to a polyamide backbone, and contain alkylamine side chains.

Claims

1. A peptide nucleic acid having formula:

##STR3## wherein;

each L is independently a naturally-occurring nucleobase or a non-naturally-occurring nucleobase;

each R^7'"'"' is independently hydrogen or C₁ -C₈ alkylamine, provided that at least one R^7'"'"' is C₁ -C₈ alkylamine;

R^h is OH, NH₂ or NHLysNH₂ ;

Rⁱ is H, COCH₃ or t-butoxycarbonyl; and

n is an integer from 1 to 30.

2. The peptide nucleic acid of claim 1 wherein at least one R^7'"'"' is C₃ -C₆ alkylamine.

3. The peptide nucleic acid of claim 2 wherein at least one R^7'"'"' is C₄ -C₅ alkylamine.

4. The peptide nucleic acid of claim 3 wherein at least one R^7'"'"' is butylamine.

5. The peptide nucleic acid of claim 4 wherein substantially all of the groups R^7'"'"' are butylamine.

6. The peptide nucleic acid of claim 1 wherein the carbon atom to which at least one substituent R^7'"'"' is attached is stereochemically enriched.

7. The peptide nucleic acid of claim 6 wherein said stereochemical enrichment is of the R configuration.

8. The peptide nucleic acid of claim 7 wherein substantially all of the groups R^7'"'"' are butylamine.

9. The peptide nucleic acid of claim 1 wherein said peptide nucleic acid is derived from an amino acid.

10. The peptide nucleic acid of claim 9 wherein said peptide nucleic acid is derived from D-lysine.

11. A pharmaceutical composition comprising a peptide nucleic acid according to claim 1 and at least one pharmaceutically acceptable carrier, binder, thickener, diluent, buffer, preservative, or surface active agent.