Skip to main content
SpringerLink
Log in

Target Biological Structures: The Cell, Organelles, DNA and RNA

  • Chapter
  • First Online:
Metallointercalators

Abstract

Living organisms are self replicating molecular factories of staggering complexity [1]. As a result, we are often overwhelmed when trying to identify potential targets for therapeutics. Water, inorganic ions and a large array of relatively small organic molecules (e.g., sugars, vitamins and fatty acids) account for approximately 80% of living matter, with water being the most abundant. Macromolecules such as proteins, polysaccharides, ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) constitute the rest. The majority of potential therapeutic targets are found within the cell. Small molecules which are vital for cellular function are imported into the cell by a variety of mechanisms but unlike smaller molecules, macromolecules are assembled within the cell itself. Drugs are usually designed to target cellular macromolecules, as they perform very specific roles in the metabolic processes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Knox I, Ladiges P, Evans B, Saint R. Biology. 2nd ed. Roseville: MaGraw Hill; 2001.

    Google Scholar 

  2. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Garland science. 5th ed. New York: Taylor and Francis Group; 2008. p. 1268.

    Google Scholar 

  3. Lodish H, Berk A, Kasier CA, Krieger M, Scott MP, Bretscher A, et al. Molecular cell biology. 6th ed. New York: W.H. Freeman and Company; 2008.

    Google Scholar 

  4. Bolsover SR, Hyams JS, Shephard EA, White HA, Wiedemann CG. Cell biology, a short course. 2nd ed. Hoboken: Wiley; 2004.

    Google Scholar 

  5. Sriram AHJW. Bioorganic chemistry: nucleic acids. Oxford: Oxford University Press; 1999.

    Google Scholar 

  6. Sarma RH. Nucleic Acid Geometry and Dynamics. New York: Pergamon; 1979, p. 424.

    Google Scholar 

  7. Watson JD, Crick FHC. Nature. 1953;171:737.

    CAS  Google Scholar 

  8. Rodger A, Nordén B. Circular dichroism and linear dichroism. 1st ed. Oxford: Oxford University Press; 1997.

    Google Scholar 

  9. Voet D, Voet JG. Biochemistry. 2nd ed. New York: Wiley; 1995.

    Google Scholar 

  10. Blackburn EH, Szostak JW. Annu Rev Biochem. 1984;53:163.

    CAS  Google Scholar 

  11. Blackburn EH. Nature. 1991;350:569.

    CAS  Google Scholar 

  12. Watson JD. Nat New Biol. 1972;239:197.

    CAS  Google Scholar 

  13. Olovnikov A. J Theor Biol. 1973;41:181.

    CAS  Google Scholar 

  14. McEachern M, Krauskopf A, Blackburn E. Annu Rev Genet. 2000;34:331.

    CAS  Google Scholar 

  15. Counter CM, Botelho FM, Wang P, Harley CB, Bacchetti S. J Virol. 1994;68:3410.

    CAS  Google Scholar 

  16. Greider CW, Blackburn EH. Cell. 1985;43:405.

    CAS  Google Scholar 

  17. Wadkins RM. Curr Med Chem. 2000;7:1.

    CAS  Google Scholar 

  18. Ying L, Wallace MI, Klenerman D. Chem Phys Lett. 2001;334:145.

    CAS  Google Scholar 

  19. Francois J-C, Thuong NT, Helene C. Nucleic Acids Res. 1994;22:3943.

    CAS  Google Scholar 

  20. Henderson PT, Armitage B, Schuster GB. Biochemistry. 1998;37:2991.

    CAS  Google Scholar 

  21. Chen F-M, Jones CM, Johnson QL. Biochemistry. 1993;32:5554.

    CAS  Google Scholar 

  22. Brown DR, Kurz M, Kearns DR, Hsu VL. Biochemistry. 1994;33:651.

    CAS  Google Scholar 

  23. Lian C, Robinson H, Wang AH. J Am Chem Soc. 1996;118:8791.

    CAS  Google Scholar 

  24. Huang H, Zhu L, Reid BR, Drobny GP, Hopkins PB. Science. 1995;270:1842.

    CAS  Google Scholar 

  25. Caradonna JP, Lippard SJ, Gait MJ, Singh M. J Am Chem Soc. 1982;104:504.

    Google Scholar 

  26. Barton JK, Lolis E. J Am Chem Soc. 1985;107:708.

    CAS  Google Scholar 

  27. Sundquiat WI, Bancroft DP, Lippard SJ. J Am Chem Soc. 1990;112:1590.

    Google Scholar 

  28. Grahman DR, Marshall LE, Reich KA, Sigman DS. J Am Chem Soc. 1980;102:5419.

    Google Scholar 

  29. Gessner RV, Quigley GJ, Wang AH-J, GAvd Marel, JHv Broom, Rich A. Biochemistry. 1985;24:237.

    CAS  Google Scholar 

  30. Record MT, Lohman TM, PJd Haseth. Mol Biol. 1976;107:145.

    CAS  Google Scholar 

  31. Robinson H, Wang AH-J. Nucleic Acids Res. 1996;24:676.

    CAS  Google Scholar 

  32. Kopka ML, Yoon C, Goodsell D, Pjura P, Dickerson RE. J Mol Biol. 1984;183:553.

    Google Scholar 

  33. Saenger W. Principles of nucleic acid structure. New York: Springer; 1984.

    Google Scholar 

  34. Pindur U, Haber M, Sattler K. J Chem Edu. 1993;70:263.

    CAS  Google Scholar 

  35. Blackburn GM, Gait MJ. Nucleic acids in chemistry and biology. 2nd ed. New York: Oxford University Press; 1996.

    Google Scholar 

  36. Berman HM, Young PR. Annu Rev Biophys Bioeng. 1981;10:87.

    CAS  Google Scholar 

  37. Werner MH, Gronenborn AM, Clore GM. Science. 1996;271:778.

    CAS  Google Scholar 

  38. Lerman LS. J Mol Biol. 1961;3:18.

    CAS  Google Scholar 

  39. Barton JK. Science. 1986;233:727.

    CAS  Google Scholar 

  40. Wilson WD, Jones RL. Adv Pharmacol Chemother. 1981;18:177.

    CAS  Google Scholar 

  41. Bauer W, Vinograd J. Basic principles in nucleic acid chemistry. New York: Academic; 1974. p. 265.

    Google Scholar 

  42. Jones RL, Lanier AL, Keel RA, Wilson WD. Nucleic Acids Res. 1980;8:1613.

    CAS  Google Scholar 

  43. Wang JC. J Mol Biol. 1974;89:783.

    CAS  Google Scholar 

  44. Cohen G, Eisenberg H. Biopolymers. 1969;8:45.

    CAS  Google Scholar 

  45. Gabbay EJ, Scofield R, Baxter CS. J Am Chem Soc. 1973;95:7850.

    CAS  Google Scholar 

  46. Saucier JM, Festy B, LePecq JB. Biochimie. 1971;53:973.

    CAS  Google Scholar 

  47. Luck G, Zimmer C, Reinert K-E, Arcamone F. Nucleic Acids Res. 1977;4:2655.

    CAS  Google Scholar 

  48. Balcarova Z, Kleinwachter V, Koudelka J, Lober G, Reinert K-E, Wakelin LPG, et al. Biophys Chem. 1978;8:27.

    CAS  Google Scholar 

  49. Dahl KS, Pardi A, Tinoco Jr I. Biochemistry. 1982;21:2730.

    CAS  Google Scholar 

  50. Banville DL, Wilson WD, Marzilli LG. Inorg Chem. 1985;24:2479.

    CAS  Google Scholar 

  51. Liu F, Meadows KA, McMilin DR. J Am Chem Soc. 1993;115:6699.

    CAS  Google Scholar 

  52. Cusumano M, Di Pietro ML, Giannetto A, Nicolo F, Rotondo E. Inorg Chem. 1998;37:563.

    CAS  Google Scholar 

  53. Zhen Q-X, Ye B-H, Zhang Q-L, Liu J-G, Li H, Ji L-N, et al. J Inorg Biochem. 1999;76:47.

    CAS  Google Scholar 

  54. Collins JG, Aldrich-Wright J, Greguric ID, Pellegrini P. Inorg Chem. 1999;38:5502.

    CAS  Google Scholar 

  55. Luedtke NW, Hwang JS, Nava E, Gut D, Kol M, Tor Y. Nucleic Acids Res. 2003;31:5732.

    CAS  Google Scholar 

  56. Brodie CR, Collins JG, Aldrich-Wright JR. Dalton Trans 2004; 1145.

    Google Scholar 

  57. Bloomfield VA, Crothers DM, Tinoco Jr I. Physical chemistry of nucleic acids. New York: Harper and Row; 1974. p. 373.

    Google Scholar 

  58. Chaires JB, Dattagupta N, Crothers DM. Biochemistry. 1982;21:3933.

    CAS  Google Scholar 

  59. Adlam G, Blagbrough IS, Taylor S, Latham HC, Haworth IS, Rodger A. Bioorg Med Chem Lett. 1994;4:2435.

    CAS  Google Scholar 

  60. Rodger A, Taylor S, Adlam G, Blagbrough IS, Haworth IS. Bioorg Med Chem. 1995;3:861.

    CAS  Google Scholar 

  61. McCoubrey A, Latham HC, Cook PR, Rodger A, Lowe G. FEBS Lett. 1996;380:73.

    CAS  Google Scholar 

  62. Choi S-D, Kim M-S, Kim SK, Lincoln P, Tuite E, Nordén B. Biochemistry. 1997;36:214.

    CAS  Google Scholar 

  63. Rodger A, Latham HC, Wormell P, Parkinson A, Ismail M, Sanders KJ. Enantiomer. 1998;3:395.

    CAS  Google Scholar 

  64. Ismail MA, Sanders KJ, Fennell GC, Latham HC, Wormell P, Rodger A. Biopolymers. 1998;46:127.

    CAS  Google Scholar 

  65. Rodger A, Sanders KJ, Hannon MJ, Meistermann I, Parkinson A, Vidler DS, et al. Chirality. 2000;12:221.

    CAS  Google Scholar 

  66. Parkinson A, Hawken M, Hall M, Sanders KJ, Rodger A. Phys Chem Chem Phys. 2000;2:5469.

    CAS  Google Scholar 

  67. Rodger A, Parkinson A, Best S. Eur J Inorg Chem. 2001;9:2311.

    Google Scholar 

  68. Patel KK, Plummer EA, Darwish M, Rodger A, Hannon MJ. J Inorg Biochem. 2002;91:220.

    CAS  Google Scholar 

  69. Lerman LS. J Cell Comp Physiol. 1964;64:1.

    CAS  Google Scholar 

  70. Crothers DM. Biopolymers. 1968;6:575.

    CAS  Google Scholar 

  71. Nordén B, Tjerneld F. Biophys Chem. 1976;4:191.

    CAS  Google Scholar 

  72. Nordén B, Tjerneld F. FEBS Lett. 1976;67:368.

    CAS  Google Scholar 

  73. Hogan M, Jardetzky O. Proc Natl Acad Sci U S A. 1979;76:6341.

    CAS  Google Scholar 

  74. Sarma RH. Nucleic acid geometry and dynamics. New York: Pergamon; 1980.

    Google Scholar 

  75. Hiort C, Nordén B, Rodger A. J Am Chem Soc. 1990;112:1971.

    CAS  Google Scholar 

  76. Halsall DJ, Rodger A, Dafforn TR. Chem Commun. 2001;23:2410.

    Google Scholar 

  77. Howe-Grant M, Wu KC, Bauer WR, Lippard SJ. Biochemistry. 1976;15:4339.

    CAS  Google Scholar 

  78. Lippard SJ, Bond PJ, Wu KC, Bauer WR. Science. 1976;194:726.

    CAS  Google Scholar 

  79. Barton JK. J Biomol Struct Dyn. 1983;1:621.

    CAS  Google Scholar 

  80. Barton JK, Danishefsky AT, Goldberg JM. J Am Chem Soc. 1984;106:2172.

    CAS  Google Scholar 

  81. Fitzsimons MP, Barton JK. J Am Chem Soc. 1997;119:3379.

    CAS  Google Scholar 

  82. Gisselfalt K, Lincoln P, Nordén B, Jonsson M. J Phys Chem B. 2000;104:3651.

    Google Scholar 

  83. Novakova O, Chen H, Vrana O, Rodger A, Sadler PJ, Brabec V. Biochemistry. 2003;42:11544.

    CAS  Google Scholar 

  84. Krugh TR, Nuss ME. Biological applications of magnetic resonance. Shulman RG, editor. New York: Academic press; 1979. p. 113.

    Google Scholar 

  85. Wilson WD, Tanious FA, Watson RA, Barton HJ, Strekowska A, Harden DB, et al. Biochemistry. 1989;28:1984.

    CAS  Google Scholar 

  86. Collins JG, Sheilds TP, Barton JK. J Am Chem Soc. 1994;116:9840.

    CAS  Google Scholar 

  87. Hudson BP, Dupureur CM, Barton JK. J Am Chem Soc. 1995;117:9379.

    CAS  Google Scholar 

  88. Odani A, Sekiguchi T, Okada H, S-i Ishiguro, Yamauchi O. Bull Chem Soc Jpn. 1995;68:2093.

    CAS  Google Scholar 

  89. Dupureur CM, Barton JK. Inorg Chem. 1997;36:33.

    CAS  Google Scholar 

  90. Greguric I, Aldrich-Wright JR, Collins JG. J Am Chem Soc. 1997;119:3621.

    CAS  Google Scholar 

  91. Franklin SJ, Treadway CR, Barton JK. Inorg Chem. 1998;37:5198.

    CAS  Google Scholar 

  92. Collins JG, Rixon R, Aldrich-Wright JR. Inorg Chem. 2000;39:4377.

    CAS  Google Scholar 

  93. Proudfoot EM, Mackay JP, Karuso P. Biochemistry. 2001;40:4867.

    CAS  Google Scholar 

  94. Greguric A, Greguric ID, Hambley TW, Aldrich-Wright JR, Collins JG. J Chem Soc Dalton Trans. 2002;6:849.

    Google Scholar 

  95. Bond PJ, Langridge R, Jennette KW, Lippard SJ. Proc Natl Acad Sci U S A. 1975;72:4825.

    CAS  Google Scholar 

  96. Sobell HM, Reddy BS, Bhandray KK, Jain SC, Sakore TD, Seshadri TP. Cold spring harbor symposia on quantitative biology, Cold Spring Harbor Lab, Cold Spring Harbor: New York; 1977. p. 87.

    Google Scholar 

  97. Lippard SJ. Acc Chem Res. 1978;11:211.

    CAS  Google Scholar 

  98. Kennard O, Hunter WN. Angew Chem Int Ed Engl. 1991;30:1245.

    Google Scholar 

  99. Bauer WR, Vinograd J. Prog Mol Subcell Biol. 1971;2:181.

    CAS  Google Scholar 

  100. Jennette KW, Lippard SJ, Vassiliades GA, Bauer WR. Proc Natl Acad Sci U S A. 1974;71:3839.

    CAS  Google Scholar 

  101. Lincoln P, Nordén B. J Phys Chem B. 1998;102:9583.

    CAS  Google Scholar 

  102. Sobell HM, Tsai C-C, Gilbert SG, Jain SC, Sakore TD. Proc Natl Acad Sci U S A. 1976;73:3068.

    CAS  Google Scholar 

  103. Pyle AM, Rehman JP, Meshoyrer R, Kumar CV, Turro NJ, Barton JK. J Am Chem Soc. 1989;111:3051.

    CAS  Google Scholar 

  104. Long EC, Barton JK. Acc Chem Res. 1990;23:271.

    CAS  Google Scholar 

  105. Mudasir N, Yoshioka H, Inoue J. Inorg Biochem. 1999;77:239.

    CAS  Google Scholar 

  106. Friedman AE, Kumar CV, Turro NJ, Barton JK. Nucleic Acids Res. 1991;19:2595.

    CAS  Google Scholar 

  107. Krotz AH, Kuo LY, Sheilds TP, Barton JK. J Am Chem Soc. 1993;115:3877.

    CAS  Google Scholar 

  108. Wang AH-J, Nathans J, Gvd Marel, JHv Boom, Rich A. Nature. 1978;276:471.

    CAS  Google Scholar 

  109. Thederahn TB, Kuwabara MD, Sigman TALDS. J Am Chem Soc. 1989;111:4941.

    CAS  Google Scholar 

  110. Hartshorn RM, Barton JK. J Am Chem Soc. 1992;114:5919.

    CAS  Google Scholar 

  111. Cusumano M, Petro MLD, Giannetto A, Nicolo F, Rotondo E. Inorg Chem. 1998;37:563.

    CAS  Google Scholar 

  112. Fisher DM, Honours Thesis, The University of Sydney (Sydney), 2000.

    Google Scholar 

  113. Wang AHJ, Nathans J, van der Marel G, van Boom JH, Rich A. Nature. 1978;276:471.

    CAS  Google Scholar 

  114. Barton JK. Science. 1986;15:8.

    Google Scholar 

  115. Capelle N, Barbet J, Dessen P, Blanquet S, Roques BP, LePecq JB. Biochemistry. 1979;18:3354.

    CAS  Google Scholar 

  116. Lowe G, Droz AS, Vilaivan T, Weaver GW, Park JJ, Pratt JM, et al. J Med Chem. 1999;42:3167.

    CAS  Google Scholar 

  117. Chan H-L, Ma D-L, Yang M, Che C-M. Chem Biol Chem. 2003;4:62.

    CAS  Google Scholar 

  118. Holmlin RE, Stemp EDA, Barton JK. Inorg Chem. 1998;230:412.

    Google Scholar 

  119. Bauer W, Vinograd J. J Mol Biol. 1970;47:419.

    CAS  Google Scholar 

  120. Gale EF, Cundliffe E, Reynolds PE, Richmond MH, Waring MJ. The molecular basis of antibiotic action. London: Wiley; 1972. p. 173.

    Google Scholar 

  121. Neidle S. Prog Med Chem. 1979;16:151.

    CAS  Google Scholar 

  122. Schwartz HS. Adv Cancer Chemother. 1979;1:1.

    CAS  Google Scholar 

  123. Denny WA. Anti-Cancer Drug Des. 1989;4:241.

    CAS  Google Scholar 

  124. Hurwitz J, Furth JJ, Malamy M, Alexander M. Proc Natl Acad Sci U S A. 1962;48:1222.

    CAS  Google Scholar 

  125. Bohner R, Hagen U. Biochim Biophys Acta. 1977;479:300.

    CAS  Google Scholar 

  126. Waring MJ. Mol Pharmacol. 1965;1:1.

    CAS  Google Scholar 

  127. Sarris AH, Niles EG, Canellakis ES. Biochim Biophys Acta. 1977;474:268.

    CAS  Google Scholar 

  128. Eron LJ, McAuslan BR. Biochim Biophys Acta. 1966;114:633.

    CAS  Google Scholar 

  129. Kanter PM, Schwartz HS. Cancer Res. 1979;39:3661.

    CAS  Google Scholar 

  130. Ross WE, Glaubiger DL, Kohn KH. Biochim Biophys Acta. 1979;562:41.

    CAS  Google Scholar 

  131. Paoletti C, Couder H, Guerineau M. Biochem Biophys Res Commun. 1972;48:950.

    CAS  Google Scholar 

  132. Deniss IS, Morgan AR. Nucleic Acids Res. 1976;3:315.

    CAS  Google Scholar 

  133. Drlica K, Franco RJ. Biochemistry. 1988;27:2253.

    CAS  Google Scholar 

  134. McCann J, Choi E, Yamasaki E, Ames BN. Proc Natl Acad Sci U S A. 1976;73:950.

    CAS  Google Scholar 

  135. Burger AM, Double JA, Konopa J, Bibby MC. Br J Cancer. 1996;74:1369.

    CAS  Google Scholar 

  136. Dziegielewski J, Skladanoski A, Konopa J. Ann Oncol. 1996;7 Suppl 1:56.

    Google Scholar 

  137. Skladanoski A, Plisov SY, Konopa J, Larsen AK. Mol Pharmacol. 1996;49:772.

    Google Scholar 

  138. Augustin E, Wheatley DN, Lamb J, Konopa J. Cancer Chemother Pharmacol. 1996;38:39.

    CAS  Google Scholar 

  139. Burger AM, Jenkins TC, Double JA, Bibby MC. Br J Cancer. 1999;81:367.

    CAS  Google Scholar 

Download references

Acknowledgements

M.P.G. and M. v H. were supported by Australian Postgraduate Awards from the University of Western Sydney. M. v H. was additionally supported by research grant funding and a College of College of Health and Science writing Scholarship. This work was supported by UWS grants and an International Science Linkage grant. We wish to thank F. Cameron and E. P Wright for useful discussions and editorial comments.

Author information

Authors and Affiliations

  1. School of Biomedical & Health Sciences, University of Western Sydney, Penrith South DC, New South Wales, Sydney, Australia

    Janice Aldrich-Wright

Authors
  1. Marcelis van Holst
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maxine P. Grant
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Janice Aldrich-Wright
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Janice Aldrich-Wright .

Editor information

Editors and Affiliations

  1. School of Biomedical & Health Sciences, University of Western Sydney, Penrith South DC, New South Wales, Australia

    Janice Aldrich-Wright

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer-Verlag/Wien

About this chapter

Cite this chapter

van Holst, M., Grant, M.P., Aldrich-Wright, J. (2011). Target Biological Structures: The Cell, Organelles, DNA and RNA. In: Aldrich-Wright, J. (eds) Metallointercalators. Springer, Vienna. https://doi.org/10.1007/978-3-211-99079-7_1

Download citation

Publish with us

Policies and ethics

Search

Navigation