Peptide nucleic acids having enhanced binding affinity and

75 Pages·2013·5.13 MB·English

‘ US005766855A
United States Patent [19] [11] Patent Number: 5,766,855
Buchardt et a]. [45] Date of Patent: Jun. 16, 1998
[54] PEPTIDE NUCLEIC ACIDS HAVING FOREIGN PATENT DOCUMENTS
ENHANCED BINDING AFFINITY AND
WO 86/05518 9/1986 WIPO .
SEQUENCE SPECIFICI'I'Y W0 90m749 3/1990 WIPO ‘
W0 9 0702 11/1992 WIPO .
[76] Inventors: Ole Buchardt, deceased. late of 3500 W0 gig?glj 3/1994 WIPO ‘
Vzerlose. Denmark; Michael Egholm.
1231 Lexington Ridge Dr.. Lexington. OTl-IER PUBLICATIONS
Mass. 02173; Peter Eigil Nielsen.
Hjortevanget 509. 2980 Kokkedal; Rolf Akashi et al.. “New Aspects of Polymer Drugs”. Adv. Polym.
Henrik Berg. Strandvaenget 6. DK Sci, 1990. 97. 108-146.
2960 Rungsted Kyst. both of Denmark; Buttrey et al.. ‘The Resolution of DL-[S-(‘I‘hymin-l-YL)
by Dorte Buchardt, executor. Alanine and Polymerisation of the [S-(Thymin-l-YL) Ala
Sondergardsvej 73. 3500 Varlose. nines”. Tetrahedron, 1975. 31. 73-75.
Germany De Koning et al.. "Unconventional Nucleotide Analogues
V. Derivatives of 6—(l-pyrimidinyl)-and 6-(9-purinyl)-2—
aminocaproic acid". Recueil, 1971. 90. 874-884.
[21] Appl. No.: 686,113
Doel et al.. “An Approach tothe Synthesis of Peptide Ana
[22] Filed: Jul. 24, 1996 logues of Oligonucleoticles (NucleopeptidesY’. Tetrahedron
Len, 1969. 27. 2285-2288.
Related US. Application Data Doel et al.. “The Synthesis of Peptides Containing Purine
and Pyrimidine Derivatives of DL-Alanine”. Tetrahedron,
[63] Continuation-impart of Ser. No. 108591, ?led as PCT! 1974. 30. 2755-2759.
EP92/01219 May 22. 1992.
(List continued on next page.)
[30] Foreign Application Priority Data
Primary Examiner—Ardin H. Marschel
x3 gz?? """"""""""" Attorney, Agent, or Firm—Woodcock Washburn Kurtz
Apr. 15. 1992 [DK] Denmark ............................... .. 0510/92 Macklcwlcz 8‘ Norms
[51] Int. Cl.6 ..................................................... .. c12Q 1/68 [57] ABSTRACT
Cl. ............................ .. A novel Class of cofnpound5_ known as peptidg nuclcic
530/300; 530/350: 536/231; 536/24.1; acids. bind complementary DNA and RNA strands more
536/243; 536/2431; 536/2432; 536/2433; strongly than a corresponding DNA strand. and exhibit
935/77; 935/78
increased sequence speci?city and binding a?inity. Methods
[58] Field Of Search ...................... .. 435/6. 1310;436/501; of increasing binding a?nity and sgquencc Speci?city of
530/300‘ 350; 536/231‘ 24‘1‘ 243-2433; peptide nucleic acids are provided wherein some peptide
935/77‘ 78 nucleic acids comprise ligands selected from a group con
sisting of naturally-occurring nucleobases and non
[56] References Cited naturally-occurring nucleobases attached to a polyamide
backbone. while other peptide nucleic acids contain at least
U.S. PATENT DOCUMENTS one 2.6-diaminopurine nucleobase and at least one C1-C8
alkylamine side chain.
5,034,506 7/1991 Summerton et a1. ................. .. 528/391
5,166,315 11/1992 Summerton et a1. 528/406
5.340.716 8/1994 Uhlman et a1. ........................... .. 435/6 24 Claims, 11 Drawing Sheets
5,766,855
Page 2
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