Probing DNA Polymerase Function with Synthetic Nucleotides

Andreas Marx; Ilka Detmer; Jens Gaster; Daniel Summerer

doi:10.1055/s-2003-44363

REVIEW

Probing DNA Polymerase Function with Synthetic Nucleotides

Andreas Marx*, Ilka Detmer, Jens Gaster, Daniel Summerer
Kekulé-Institut für Organische Chemie und Biochemie, Universität Bonn, Gerhard-Domagk-Str. 1, 53121 Bonn, Germany
Fax: +49(228)735388; e-Mail: a.marx@uni-bonn.de;

Abstract

All articles of this category

Abstract

Transmission of the genetic information from the parental DNA strand to the offspring is crucial for the survival of any living species. In nature this process is catalyzed by the replication machinery in which DNA polymerases are essential for the entire DNA synthesis. Recently, a wealth of valuable new insights into DNA polymerase mechanisms were gained through application of carefully designed synthetic nucleotides and oligonucleotides in functional enzyme studies. The applied analogues exhibit features that differ in certain aspects from their natural counterparts and thus, allow investigation of the involvement and efficacy of a chosen particular aspect on the entire complex enzyme mechanism. This review will focus on a depiction of the synthetic efforts that were undertaken towards the targeted synthesis of nucleotide analogues with carefully altered properties. The synthetic endeavors will be discussed in the context of the motivation and the problem under investigation.

1 Introduction
2 Functional DNA Polymerase Studies
3 Modified Substrates for Investigation of DNA Polymerase Function
3.1 Nucleobase Modifications
3.1.1 Rearrangement of Nucleobase Hydrogen Bonding Patterns
3.1.2 Deleting Nucleobase Hydrogen Bonding Acceptors and/or Donors
3.1.3 Non-Nucleoside Surrogates
3.2 Modification at the 2′-Deoxyribose Moiety
4 Outlook

Key words

DNA - nucleosides - nucleotides - oligonucleotides - DNA polymerases

Full Text

References

1 Kornberg A. Baker TA. DNA Replication 2nd ed.: W. H. Freeman and Company; New York: 1991.

2a Joyce CM. Steitz TA. Annu. Rev. Biochem. 1994, 63: 777-822

2b Steitz TA. Smerdon SJ. Jäger J. Joyce CM. Science 1994, 266: 2022

Reviews:

3a Kool ET. Annu. Rev. Biochem. 2002, 71: 191

3b Patel PH. Loeb LA. Nat. Struct. Biol. 2001, 8: 656

3c Kunkel TA. Bebenek K. Annu. Rev. Biochem. 2000, 69: 497

3d Kool ET. Morales JC. Guckian KM. Angew. Chem. Int. Ed. 2000, 39: 991

3e Kunkel TA. Wilson SH. Nat. Struct. Biol. 1998, 5: 95

3f Diederichsen U. Angew. Chem. Int. Ed. 1998, 37: 1655

3g Goodman MF. Proc. Natl. Acad. Sci. U.S.A. 1997, 94: 10493

3h Echols H. Goodman MF. Annu. Rev. Biochem. 1991, 60: 477

Reviews:

4a Goodman MF. Annu. Rev. Biochem. 2002, 71: 17

4b Hübscher U. Maga G. Spadari S. Annu. Rev. Biochem. 2002, 71: 133

4c Marx A. Summerer D. ChemBioChem 2002, 3: 405

4d Friedberg EC. Fischhaber PL. Kisker C. Cell 2001, 107: 9

4e Livneh Z. J. Biol. Chem. 2001, 276: 25639

4f Goodman MF. Tippin B. Nat. Rev. Mol. Cell Biol. 2000, 1: 101

4g Hübscher U. Nasheuer HP. Syvaoja JE. Trends Biochem. Sci. 2000, 25: 143

4h Friedberg EC. Feaver WJ. Gerlach VL. Proc. Natl. Acad. Sci. U.S.A. 2000, 97: 5681

4i Friedberg EC. Gerlach VL. Cell 1999, 98: 413

4j Johnson RE. Washington MT. Prakash S. Prakash L. Proc. Natl. Acad. Sci. U.S.A. 1999, 100: 3895

5a Johnson SJ. Taylor JS. Beese LS. Proc. Natl. Acad. Sci. U.S.A. 2003, 96: 12224

5b Silvian LF. Toth EA. Pham P. Goodman MF. Ellenberger T. Nat. Struct. Biol. 2001, 8: 984

5c Zhou B.-L. Pata JD. Steitz TA. Mol. Cells 2001, 8: 427

5d Trincao J. Johnson RE. Escalante CR. Prakash S. Prakash L. Aggarwal AK. Mol. Cells 2001, 8: 417

5e Boudsocq H. Ling F. Woodgate R. Yang W. Cell 2001, 107: 91

5f Franklin MC. Wang J. Steitz TA. Cell 2001, 98: 413

5g Doublié S. Tabor S. Long AM. Richardson CC. Ellenberger T. Nature (London, U.K.) 1998, 391: 251

5h Korolev Y. Li S. Waksman G. EMBO J. 1998, 17: 7514

5i Kiefer JR. Mao C. Braman JC. Beese LS. Nature (London, U.K.) 1998, 391: 304

5j Huang HF. Chopra R. Verdine GL. Harrison SC. Science(Washington, DC, U. S.) 1998, 282: 1669

5k Ollis DL. Brick P. Hamlin R. Xuong NG. Steitz TA. Nature (London, U.K.) 1985, 313: 762

6a Creighton S. Bloom LB. Goodman MF. Methods Enzymol. 1995, 262: 232

6b Goodman MF. Creighton S. Bloom LB. Petruska J. Crit. Rev. Biochem. Mol. Biol. 1993, 28: 83

7 A recent application: Harris VH. Smith CL. Cummins WJ. Hamilton AL. Hornby DP. Williams DW. Org. Biomol. Chem. 2003, 1: 2070

8 Hübscher U. Spadari S. Physiol. Rev. 1994, 74: 259

9 Ichikawa E. Kato K. Curr. Med. Chem. 2001, 8: 385

10 Thum O. Jäger S. Famulok M. Angew. Chem. Int. Ed. 2001, 40: 3990

Recent reviews:

11a Verma S. Jäger S. Thum O. Famulok M. Chem. Rec. 2003, 3: 51

11b Bittker JA. Phillips KJ. Liu DR. Curr. Opin. Chem. Biol. 2002, 6: 367

12a Brakmann S. Lobermann S. Angew. Chem. Int. Ed. 2001, 40: 1427

12b Brakmann S. Nieckchen P. ChemBioChem 2001, 2: 773

12c Zink D. Cremer T. Saffrich R. Fischer R. Trendelenburg MF. Ansorg W. Stelzer EHK. Hum. Genet. 1998, 102: 241

13a Switzer C. Moroney SE. Benner SA. J. Am. Chem. Soc. 1989, 111: 8322

13b Piccirilli JA. Krauch T. Moroney SE. Benner SA. Nature (London, U.K.) 1990, 343: 103

13c Bain JD. Switzer SE. Chamberlin AR. Benner SA. Nature (London, U.K.) 1992, 356: 537

13d Horlacher J. Hottiger M. Podust VN. Hübscher U. Benner SA. Proc. Natl. Acad. Sci. U.S.A. 1995, 92: 6329

13e Lutz MJ. Held HA. Hottiger M. Hübscher U. Benner SA. Nucleic Acids Res. 1996, 24: 1308

14a Seela F. Gabler B. Helv. Chim. Acta 1994, 77: 622

14b Kazimierczuk Z. Mertens R. Kawczynski W. Seela F. Helv. Chim. Acta 1991, 74: 1742

14c Seela F. Wei C. Helv. Chim. Acta 1997, 80: 73

14d Seela F. Mertens R. Kazimierczuk Z. Helv. Chim. Acta 1992, 75: 2298

15a Roberts C. Bandaru R. Switzer C. J. Am. Chem. Soc. 1997, 119: 4640

15b Roberts C. Bandaru R. Switzer C. Tetrahedron Lett. 1995, 36: 3601

16 Jurczyk SC. Kodra JT. Park J.-H. Benner SA. Battersby TR. Helv. Chim. Acta 1999, 82: 1005

17 Ludwig J. Eckstein F. J. Org. Chem. 1989, 54: 631

18

See comments in ref. [13a] and ref. [19] .

19 Tor Y. Dervan PB. J. Am. Chem. Soc. 1993, 115: 4461

20 Strazewski P. Tamm C. Angew. Chem., Int. Ed. Engl. 1990, 29: 36

21 Charczuk R. Tamm C. Suri B. Bickle TA. Nucleic Acids Res. 1986, 14: 9530

22 Hirao I. Ohtsuki T. Mitsui T. Yokoyama S. J. Am. Chem. Soc. 2000, 112: 6118

23a Hsieh H.-P. McLaughlin LW. J. Org. Chem. 1995, 60: 5356

23b Daves GD. Acc. Chem. Res. 1990, 23: 201

24 Guo M.-J. Hildbrand S. Leumann CJ. McLaughlin LW. Waring MJ. Nucleic Acids Res. 1998, 26: 1863

25 Hildbrand S. Leumann CJ. Angew. Chem. Int. Ed. 1996, 35: 1968

26a Krohn K. Heins H. Wielckens K. J. Med. Chem. 1992, 35: 511

26b Kraus GA. Molina MT. J. Org. Chem. 1988, 53: 752

27 Fraley AW. Chen D. Johnson K. McLaughlin LW. J. Am. Chem. Soc. 2003, 125: 616

28a Spratt TE. Campbell CR. Biochemistry 1994, 33: 11364

28b Spratt TE. de los Santos H. Biochemistry 1992, 31: 3688

29a Krenitsky TA. Koszalka GW. Tuttle JV. Biochemistry 1981, 20: 3615

29b Krenitsky TA. Rideout JL. Chao EY. Koszalka GW. Gurney F. Crouch RC. Cohn NK. Wolberg G. Vinegar R. J. Med. Chem. 1986, 29: 138

30 Spratt TE. Biochemistry 2001, 40: 2647

31 Washington MT. Wolfle WT. Spratt TE. Prakash L. Prakash S. Proc. Natl. Acad. Sci. U.S.A. 2003, 100: 5113

32 Ren RX.-F. Chaudhuri NC. Paris PL. Rumney IVS. Kool ET. J. Am. Chem. Soc. 1996, 118: 7671

33 Moran S. Ren RX.-F. Rumney IVS. Kool ET. J. Am. Chem. Soc. 1997, 119: 2056

34 Moran S. Ren RX.-F. Kool ET. Proc. Natl. Acad. Sci. U.S.A. 1997, 94: 10506

35 Morales JC. Kool ET. Nat. Struct. Biol. 1998, 5: 950

36 Matray TJ. Kool ET. Nature (London, U.K.) 1999, 399: 704

37 Morales JC. Kool ET. J. Am. Chem. Soc. 2000, 121: 2323

38 Kovács T. Ötvös L. Tetrahedron Lett. 1988, 29: 4525

39 Morales JC. Kool ET. J. Am. Chem. Soc. 2000, 122: 1001

40a Matsuda S. Henry AA. Schultz PG. Romesberg FE. J. Am. Chem. Soc. 2003, 125: 6134

40b Yu C. Henry AA. Romesberg FE. Schultz PG. Angew. Chem. Int. Ed. 2002, 41: 3841

40c Tae EL. Wu Y. Xia G. Schultz PG. Romesberg FE. J. Am. Chem. Soc. 2001, 123: 7439

40d Ogawa AK. Wu Y. Berger M. Schultz PG. Romesberg FE. J. Am. Chem. Soc. 2000, 122: 8803

40e Ogawa AK. Wu Y. McMinn DL. Liu J. Schultz PG. Romesberg FE. J. Am. Chem. Soc. 2000, 122: 3274

40f Wu Y. Ogawa AK. Berger M. McMinn DL. Liu J. Schultz PG. Romesberg FE. J. Am. Chem. Soc. 2000, 122: 7621

40g McMinn DL. Ogawa AK. Wu Y. Liu J. Schultz PG. Romesberg FE. J. Am. Chem. Soc. 1999, 121: 11585

41a Marx A. Spichty M. Amacker M. Schwitter U. Hübscher U. Bickle TA. Maga G. Giese B. Chem. Biol. 1999, 6: 111

41b Marx A. Amacker M. Stucki M. Hübscher U. Bickle TA. Giese B. Nucleic Acids Res. 1998, 26: 4063

41c Marx A. MacWilliams MP. Bickle TA. Schwitter U. Giese B. J. Am. Chem. Soc. 1997, 119: 1131

41d Hess MT. Schwitter U. Petretta M. Giese B. Naegeli H. Biochemistry 1997, 36: 2332

41e Marx A. Erdmann P. Senn M. Körner S. Jungo T. Petretta M. Imwinkelried P. Dussy A. Kulicke KJ. Macko L. Zehnder M. Giese B. Helv. Chim. Acta 1996, 79: 1980

42a Summerer D. Marx A. Angew. Chem. Int. Ed. 2001, 40: 3693

42b Strerath M. Cramer J. Restle T. Marx A. J. Am. Chem. Soc. 2002, 124: 11230

42c Cramer J. Strerath M. Marx A. Restle T. J. Biol. Chem. 2002, 277: 43593

42d Summerer D. Marx A. J. Am. Chem. Soc. 2002, 124: 910

42e Strerath M. Marx A. Angew. Chem. Int. Ed. 2002, 41: 4766

42f Strerath M. Summerer D. Marx A. ChemBioChem 2002, 3: 578

43a Detmer I. Summerer D. Marx A. Chem. Commun. 2002, 2314

43b Detmer I. Summerer D. Marx A. Eur. J. Org. Chem. 2003, 1837

44a Vastmans K. Pochet S. Peys A. Kerremans L. Van Aerschot A. Hendrix C. Marlière P. Herdewijn PB. Biochemistry 2000, 39: 12757

44b Vastmans K. Froeyen M. Kerremans L. Pochet S. Herdewijn PB. Nucleic Acids Res. 2001, 29: 3154

45 De Bouvere B. Kerremans L. Rozenski J. Janssen G. Van Aerschot A. Claes P. Busson R. Herdewijn PB. Liebig Ann. Recl. 1997, 1453

46a Chaput JC. Ichida JK. Szostak JW. J. Am. Chem. Soc. 2003, 125: 856

46b Chaput JC. Szostak JW. J. Am. Chem. Soc. 2003, 125: 9274

47 Schöning K.-U. Scholz P. Guntha S. Wu X. Krishnamurthy R. Eschenmoser A. Science 2000, 290: 1347

48a Burgers PMJ. Eckstein F. J. Biol. Chem. 1979, 254: 6889

48b Brody RS. Frey PA. Biochemistry 1981, 20: 1245

49a Alexandrova LA. Skoblov AY. Jasko MV. Victorova LS. Krayevsky AA. Nucleic Acids Res. 1998, 26: 778

49b Dineva MA. Chakurov S. Bratovanova EK. Devedjiev I. Petkov DD. Bioorg. Med. Chem. 1993, 1: 411

50a He K. Porter KW. Hasan A. Briley JD. Shaw BR. Nucleic Acids Res. 1999, 27: 1788

50b Li H. Porter K. Huang F. Shaw BR. Nucleic Acids Res. 1995, 23: 4495