Peptide nucleic acids having enhanced binding affinity, sequence

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Peptide Nucleic Acids Having Enhanced Binding Affinity, Sequence Specificity and
Solubility
Buchardt, Ole; Engholm, Michael; Nielsen, Peter E.; Berg, Rolf Henrik
Publication date:
1998
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Citation (APA):
Buchardt, O., Engholm, M., Nielsen, P. E., & Berg, R. H. (1998). Peptide Nucleic Acids Having Enhanced
Binding Affinity, Sequence Specificity and Solubility. (Patent No. US5736336).

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US005736336A
United States Patent [19] [11] Patent Number: 5,736,336
Buchardt et al. [45] Date of Patent: Apr. 7, 1998
[54] PEPTIDE NUCLEIC ACIDS HAVING 5,340,716 8/1994 Uhlman et a1. ........................... .. 435/6
ENHANCED BINDING AFFINITY,
SEQUENCE SPECIFICITY AND SOLUBILITY FOREIGN PAIEM DOCUMEN 15
WO 86/05518 9/1986 WIPO .
[76] Inventors: Ole Buchardt, deceased. late of WO 90/02749 3/1990 WIPO .
Varlpse, Denmark; by Dorte WO 92120702 11/1992 WIPO ,
S¢ndergardsvej 73. 3500 V?rl?se. OTHER PUBLICATIONS
Denmark; Michael Egholm. 1231
Lexington Rjdgc Dru Lmington~ Mass_ Akaslu' et al.. “New Aspects of Polymer Drugs”. Adv. Polym.
02173; peter Eigil Nielsen. Sci, 1990. 97. 108-146. .
Hjomvznget 509, 2980 KokkedaL Buttrey et al., ‘The Resolution of DL-B-(Thyrmn-l-YL)
Denmark; Rolf Henrik Bel-g Alanine and Polymerisation of the B-(Thymin-l-YL) Ala
Strandvaenget 6, DK 2960 Rungsted nines‘: Tetrahedron- 19'75- 31_- 73'75- _
Kyst. Denmark De Koning et al.. “Unconventional Nucleotlde Analogues V.
Derivatives of 6—(1—pyrimidiny1)—and
_ 6-(9-purinyl)-2-a.rninocaproic aci ". Recueil, 1971. 90.
[21] Appl. No.. 847,108 874_884.
[22] Filed: May 1, 1997 Doel et al.. “An Approach to the Synthesis of Peptide
Analogues of oligonucleotides (Nucleopep’n'desy’, Tetrahe
Related US. Application Data dron Lett., 1969. 27. 2285-2288.
Doel et al.. ‘The Synthesis of Peptides Containing Purine
[60] Division _of _Ser. No. 686,116, Jul. 24, 1996, which is a and pyrimidine Derivatives of DL_A1am'n¢”_ Tetrahedron,
contmuanon-m-part of Ser. No. 108,591, Nov. 22, 1993. 1974‘ 30, 2755__2759_
[30] Foreign Application Priority Data (List continued on next page.)
May 24, 1991 [DK] Denmark DK 0986/91 Primary Examiner-Ardin H. Marschel
May 24, 1991 [DK] Denmark
Attorney Agent, or Firm—Woodcock Washburn Kurtz
Apr. 15, 1992 [DK] Denmark ........................ DK 0510/92
Mackiewicz & Norris LLP
[51] Int. Cl.6 .. .... .. C12Q 1/68; C07K 5/00 [57] ABSTRACT
[52] us. Cl. ............................ .. 435/6; 436/501; 530/300;
530/333; 530/350; 536/231; 536/24.1; A novel class of compounds. known as peptide nucleic
536/243; 536/2431; 536/2432; 536/2433; acids. bind complementary DNA and RNA strands more
536/253; 935/77; 935/78 strongly than a corresponding DNA strand, and exhibit
[58] Field ofSearch ...................... .. 435/6, 810; 436/501; increased sequence speci?city and solubility. The peptide
530/300. 333. 350; 536/231. 24.1. 24.3. nucleic acids comprise ligands selected from a group con
33. 25.3; 935/77. 78 sisting of naturally-occurring nucleobases and non
naturally-oocun'lng nucleobases attached to a polyamide
[56] References Cited backbone, and contain C PCS alkylamine side chains. Meth
ods of enhancing the solubility. binding a?inity and
U.S. PATENT DOCUMENTS
sequence speci?city of PNAs are provided.
5,034,506 7/1991 Summertonet al. ................. .. 528/391
5,166,315 11/1992 Summertonetal. ................. .. 528/406 20 Claims, 11 Drawing Sheets
BODeNACHD + H,"
H (W4
16 hill-t
5,736,336
Page 2
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US. Patent Apr. 7, 1998 Sheet 1 of 11 5,736,336

US. Patent Apr. 7, 1998 Sheet 3 of 11 5,736,336
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