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PMID: 17309194 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Synthesis and properties of size-expanded DNAs: toward designed, functional genetic systems.

Accounts of chemical research ·Vol. 40 ·No. 2 ·2007-02-00 ·Pages 141-50

Krueger AT, Lu H, Lee AH, Kool ET

Abstract

We describe the design, synthesis, and properties of DNA-like molecules in which the base pairs are expanded by benzo homologation. The resulting size-expanded genetic helices are called xDNA ("expanded DNA") and yDNA ("wide DNA"). The large component bases are fluorescent, and they display high stacking affinity. When singly substituted into natural DNA, they are destabilizing because the benzo-expanded base pair size is too large for the natural helix. However, when all base pairs are expanded, xDNA and yDNA form highly stable, sequence-selective double helices. The size-expanded DNAs are candidates for components of new, functioning genetic systems. In addition, the fluorescence of expanded DNA bases makes them potentially useful in probing nucleic acids.

MeSH Terms
Base Pairing Base Sequence Benzene Derivatives/chemistry DNA/chemical synthesis,chemistry,genetics DNA-Directed DNA Polymerase/chemistry,metabolism Fluorescence Magnetic Resonance Spectroscopy Models, Chemical Nucleic Acid Conformation Nucleic Acid Probes Spectrometry, Fluorescence
Chemicals
Benzene Derivatives Nucleic Acid Probes DNA DNA-Directed DNA Polymerase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Krueger Andrew T
Department of Chemistry, Stanford University, Stanford, California 94305, USA.
Lu Haige
Lee Alex H F
Kool Eric T
References (56)
56 references, click to expand
  1. TNA synthesis by DNA polymerases.
    J Am Chem Soc. 2003 Aug 6;125(31):9274-5 PMID: 12889939
  2. The structure of DNA.
    Cold Spring Harb Symp Quant Biol. 1953;18:123-31 PMID: 13168976
  3. Mimicking the Structure and Function of DNA: Insights into DNA Stability and Replication.
    Angew Chem Int Ed Engl. 2000 Mar;39(6):990-1009 PMID: 10760910
  4. Stacking and stability of RNA duplexes containing fluorobenzene and fluorobenzimidazole nucleosides.
    Nucleosides Nucleotides Nucleic Acids. 2001 Apr-Jul;20(4-7):815-8 PMID: 11563122
  5. Probing the active site tightness of DNA polymerase in subangstrom increments.
    Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):15803-8 PMID: 16249340
  6. Size-expanded analogues of dG and dC: synthesis and pairing properties in DNA.
    J Org Chem. 2005 Jan 21;70(2):639-47 PMID: 15651812
  7. Base-flipping mutations of uracil DNA glycosylase: substrate rescue using a pyrene nucleotide wedge.
    Biochemistry. 2002 Sep 17;41(37):11248-54 PMID: 12220190
  8. A new four-base genetic helix, yDNA, composed of widened benzopyrimidine-purine pairs.
    J Am Chem Soc. 2005 Mar 16;127(10):3332-8 PMID: 15755149
  9. Nucleotide analogues as probes for DNA polymerases.
    Cell Mol Life Sci. 2005 Sep;62(18):2080-91 PMID: 16041567
  10. Efficient incorporation of a copper hydroxypyridone base pair in DNA.
    J Am Chem Soc. 2002 Oct 23;124(42):12494-8 PMID: 12381191
  11. A third base pair for the polymerase chain reaction: inserting isoC and isoG.
    Nucleic Acids Res. 2004;32(6):1937-41 PMID: 15051811
  12. 5'-Tethered stilbene derivatives as fidelity- and affinity-enhancing modulators of DNA duplex stability.
    J Am Chem Soc. 2004 Apr 21;126(15):4762-3 PMID: 15080664
  13. Replication of the base pair 6-thioguanine/5-methyl-2-pyrimidine with the large Klenow fragment of Escherichia coli DNA polymerase I.
    Biochemistry. 1993 Mar 30;32(12):3047-57 PMID: 8457565
  14. Toward a new genetic system with expanded dimensions: size-expanded analogues of deoxyadenosine and thymidine.
    J Am Chem Soc. 2004 Feb 4;126(4):1102-9 PMID: 14746479
  15. Simple fluorescent pyrimidine analogues detect the presence of DNA abasic sites.
    J Am Chem Soc. 2005 Aug 10;127(31):10784-5 PMID: 16076156
  16. Synthetic biology: Act natural.
    Nature. 2003 Jan 9;421(6919):118 PMID: 12520282
  17. Synthesis and biochemical evaluation of 2'-deoxy-lin-benzoadenosine phosphates.
    Biochemistry. 1984 Aug 14;23(17):3868-73 PMID: 6487584
  18. Efforts towards expansion of the genetic alphabet: pyridone and methyl pyridone nucleobases.
    Angew Chem Int Ed Engl. 2006 Jun 26;45(26):4326-9 PMID: 16733840
  19. Beyond A, C, G and T: augmenting nature's alphabet.
    Curr Opin Chem Biol. 2003 Dec;7(6):727-33 PMID: 14644182
  20. Synthesis and antitumor activity of thieno-separated tricyclic purines.
    J Med Chem. 2000 Dec 14;43(25):4877-83 PMID: 11123997
  21. Experimental Measurement of Aromatic Stacking Affinities in the Context of Duplex DNA.
    J Am Chem Soc. 1996 Aug 28;118(34):8182-8183 PMID: 20882117
  22. Expanded-size bases in naturally sized DNA: evaluation of steric effects in Watson-Crick pairing.
    J Am Chem Soc. 2004 Sep 29;126(38):11826-31 PMID: 15382917
  23. Defined dimensional changes in enzyme cofactors: fluorescent "stretched-out" analogs of adenine nucleotides.
    Science. 1977 Jan 21;195(4275):296-8 PMID: 188137
  24. Assembly of the complete eight-base artificial genetic helix, xDNA, and its interaction with the natural genetic system.
    Angew Chem Int Ed Engl. 2005 May 13;44(20):3118-22 PMID: 15834852
  25. Benzoquinazoline derivatives as substitutes for thymine in nucleic acid complexes. Use of fluorescence emission of benzo[g]quinazoline-2,4-(1H,3H)-dione in probing duplex and triplex formation.
    Biochemistry. 1998 Sep 29;37(39):13765-75 PMID: 9753465
  26. New method for scanning of single-nucleotide polymorphisms (SNPs): recognition of guanine-guanine mismatches by dimeric naphthyridine.
    Nucleic Acids Symp Ser. 2000;(44):119-20 PMID: 12903297
  27. Enzymatic recognition of the base pair between isocytidine and isoguanosine.
    Biochemistry. 1993 Oct 5;32(39):10489-96 PMID: 7691174
  28. Polycyclic aromatic DNA-base surrogates: high-affinity binding to an adenine-specific base-flipping DNA methyltransferase.
    Angew Chem Int Ed Engl. 2003 Aug 25;42(33):3958-60 PMID: 12949880
  29. A four-base paired genetic helix with expanded size.
    Science. 2003 Oct 31;302(5646):868-71 PMID: 14593180
  30. Clear distinction of purine bases on the complementary strand by a fluorescence change of a novel fluorescent nucleoside.
    J Am Chem Soc. 2003 Apr 30;125(17):4972-3 PMID: 12708835
  31. Size-expanded DNA bases: an ab initio study of their structural and electronic properties.
    J Phys Chem B. 2005 Nov 10;109(44):21135-9 PMID: 16853737
  32. Varying DNA base-pair size in subangstrom increments: evidence for a loose, not large, active site in low-fidelity Dpo4 polymerase.
    Biochemistry. 2006 Mar 7;45(9):2772-8 PMID: 16503632
  33. Fluorinated DNA bases as probes of electrostatic effects in DNA base stacking.
    Angew Chem Int Ed Engl. 2003 Dec 15;42(48):5973-7 PMID: 14679546
  34. Base-stacking and base-pairing contributions to helix stability: thermodynamics of double-helix formation with CCGG, CCGGp, CCGGAp, ACCGGp, CCGGUp, and ACCGGUp.
    Biochemistry. 1983 Jan 18;22(2):256-63 PMID: 6824629
  35. Solution structure of xDNA: a paired genetic helix with increased diameter.
    J Am Chem Soc. 2004 Jun 9;126(22):6900-5 PMID: 15174859
  36. Enzymatic incorporation of a new base pair into DNA and RNA extends the genetic alphabet.
    Nature. 1990 Jan 4;343(6253):33-7 PMID: 1688644
  37. Defined dimensional changes in enzyme substrates and cofactors. Synthesis of lin-benzoadenosine and enzymatic evaluation of derivatives of the benzopurines.
    J Am Chem Soc. 1976 Jun 23;98(13):3987-94 PMID: 819479
  38. Novel benzopyrimidines as widened analogues of DNA bases.
    J Org Chem. 2005 Jan 7;70(1):132-40 PMID: 15624915
  39. Recognition by viral and cellular DNA polymerases of nucleosides bearing bases with nonstandard hydrogen bonding patterns.
    Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6329-33 PMID: 7541538
  40. A two-unnatural-base-pair system toward the expansion of the genetic code.
    J Am Chem Soc. 2004 Oct 20;126(41):13298-305 PMID: 15479084
  41. Synthesis of fluorescent nucleotide analogues: 5'-mono-, di-, and triphosphates of linear-benzoguanosine, linear-benzoinosine, and linear-benzoxanthosine.
    Proc Natl Acad Sci U S A. 1979 Sep;76(9):4262-4 PMID: 291962
  42. Size-expanded yDNA bases: an ab initio study.
    J Phys Chem B. 2006 Mar 30;110(12):6379-84 PMID: 16553457
  43. Synthesis of 1,8-naphthyridine C-nucleosides and their base-pairing properties in oligodeoxynucleotides: thermally stable naphthyridine:imidazopyridopyrimidine base-pairing motifs.
    Angew Chem Int Ed Engl. 2005 Jan 14;44(4):596-8 PMID: 15612071
  44. Active site tightness and substrate fit in DNA replication.
    Annu Rev Biochem. 2002;71:191-219 PMID: 12045095
  45. A novel silver(i)-mediated DNA base pair.
    J Am Chem Soc. 2002 Nov 20;124(46):13684-5 PMID: 12431092
  46. Exploring the limits of DNA size: naphtho-homologated DNA bases and pairs.
    J Am Chem Soc. 2006 Jul 19;128(28):9219-30 PMID: 16834396
  47. New base pairing motifs. The synthesis and thermal stability of oligodeoxynucleotides containing imidazopyridopyrimidine nucleosides with the ability to form four hydrogen bonds.
    J Am Chem Soc. 2003 Aug 20;125(33):9970-82 PMID: 12914460
  48. yDNA: a new geometry for size-expanded base pairs.
    Angew Chem Int Ed Engl. 2004 Nov 5;43(43):5834-6 PMID: 15523708
  49. Large stacking stability of a base pair-mimic nucleotide on the DNA duplex.
    Nucleic Acids Res Suppl. 2003;(3):79-80 PMID: 14510389
  50. Detection of single base mismatches and abasic sites using phenanthridinium as an artificial DNA base and charge donor.
    Org Biomol Chem. 2005 Jan 7;3(1):36-8 PMID: 15602596
  51. Base-discriminating fluorescent (BDF) nucleoside: distinction of thymine by fluorescence quenching.
    Chem Commun (Camb). 2004 Aug 7;(15):1704-5 PMID: 15278146
  52. Fluorescent properties of DNA base analogue tC upon incorporation into DNA--negligible influence of neighbouring bases on fluorescence quantum yield.
    Nucleic Acids Res. 2005;33(16):5019-25 PMID: 16147985
  53. DNA polymerase template interactions probed by degenerate isosteric nucleobase analogs.
    Chem Biol. 2003 Sep;10(9):815-25 PMID: 14522052
  54. Fluorescence studies of nucleotides and polynucleotides. I. Formycin, 2-aminopurine riboside, 2,6-diaminopurine riboside, and their derivatives.
    J Biol Chem. 1969 Mar 10;244(5):1228-37 PMID: 5767305
  55. DNA replication fidelity.
    Annu Rev Biochem. 2000;69:497-529 PMID: 10966467
  56. A universal nucleoside for use at ambiguous sites in DNA primers.
    Nature. 1994 Jun 9;369(6480):492-3 PMID: 8202140
Article Info
Journal
Accounts of chemical research
Abbr.
Acc Chem Res
ISSN
0001-4842
DOI
10.1021/ar068200o
Published
2007-02-00
Pages
141-50
Language
English
Region
United States
NLM ID
0157313
PMCID
PMC2539066
Subset
IM
Grants
NIGMS NIH HHS · R01 GM063587-05 · United States
NIGMS NIH HHS · R01 GM063587 · United States
NIGMS NIH HHS · R01 GM063587-07 · United States
NIGMS NIH HHS · GM 63587 · United States
NIGMS NIH HHS · R01 GM063587-06 · United States
NIGMS NIH HHS · R01 GM063587-07S1 · United States
External Links
PubMed source DOI: 10.1021/ar068200o PMC Full Text View journal details
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