Metallopharmaceuticals I: DNA Interactions by Andrew Gelasco, Stephen J. Lippard (auth.), Professor

By Andrew Gelasco, Stephen J. Lippard (auth.), Professor Michael J. Clarke, Professor Peter J. Sadler (eds.)

Inorganic compounds provide a lot scope for the layout of novel and healing brokers. The frequent use of paramagnetic steel complexes as powerful distinction brokers for magnetic resonsance imaging (e.g. Gd) demonstrates that the toxicity of metals might be finely managed through the approriate selection of ligands. The winning focusing on of radioisotopes back is determined by ligand layout and steel oxidation country. Bismuth and gold complexes have lengthy been utilized in drugs yet just recently have advances been made in figuring out the molecular foundation in their mechanism of motion. New parts with medical strength comprise using polyoxometallates and fullerenes as antiviral brokers and vanadium complexes as insulin mimetics.

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1, but significantly disrupts local base pairing and stacking at the 5' -side of the adduct. The platinum lesion causes a severe roll ofthe 5'-guanine base (G6) towards the major groove. The large propeller twist of -81 ° at the G6-step causes a disruption of the hydrogen bonds to C21. The intervening base T7 is no longer base-paired to A20 and stacks under the distorted G6* base, pushing the thymine ring into the minor groove opposite the platinum adduct. This type of structure had previously been predicted for a related 1,3-intrastrand trans-DDP adduct [84].

49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. 64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85. 86. 87. A. }. Lippard Gelasco A, Lippard SJ (1998) Biochernistry 37:9230 Dunham SU, Dunham SU, Turner q, Lippard SJ (1998) J Am Chern Soc 120:5395 Johnson NP, Hoeschele JD, Rahn RO (1980) Chern-Biol Interactions 30:151 Bancroft DP, Lepre CA, Lippard SJ (1990) J Am Chern Soc 112:6860 Orton DM, Gretton VA, Green M (1993) Inorg Chim Acta 204:265 Fichtinger-Scheprnan AMJ, Lohman PHM, Reedijk J (1982) Nucleic Acids Res 10:5345 Elrnroth SKC, Lippard SJ (1994) J Am Chern Soc 116:3633 Hambley TW (1997) Coord Chern Rev 166:181 Bloernink MJ, Reedijk J (1996) Cisplatin and derived anticancer drugs: rnechanisrn and current status of DNA binding.

78. 79. 80. 81. 82. 83. 84. 85. 86. 87. A. }. Lippard Gelasco A, Lippard SJ (1998) Biochernistry 37:9230 Dunham SU, Dunham SU, Turner q, Lippard SJ (1998) J Am Chern Soc 120:5395 Johnson NP, Hoeschele JD, Rahn RO (1980) Chern-Biol Interactions 30:151 Bancroft DP, Lepre CA, Lippard SJ (1990) J Am Chern Soc 112:6860 Orton DM, Gretton VA, Green M (1993) Inorg Chim Acta 204:265 Fichtinger-Scheprnan AMJ, Lohman PHM, Reedijk J (1982) Nucleic Acids Res 10:5345 Elrnroth SKC, Lippard SJ (1994) J Am Chern Soc 116:3633 Hambley TW (1997) Coord Chern Rev 166:181 Bloernink MJ, Reedijk J (1996) Cisplatin and derived anticancer drugs: rnechanisrn and current status of DNA binding.

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