2. POLYNUCLEAR PLATINUM COMPLEXES. STRUCTURAL DIVERSITY AND DNA BINDING
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Viktor Brabec
Abstract
Polynuclear platinum complexes (PPCs) represent a discrete structural class of DNA-binding agents with excellent antitumor properties. The use of at least two platinum coordinating units automatically means that multifunctional DNA binding modes are possible. The structural variability inherent in a polynuclear platinum structure can be harnessed to produce discrete modes of DNA binding, with conformational changes distinct from and indeed inaccessible to, the mononuclear agents such as cisplatin. Since our original contributions in this field a wide variety of dinuclear complexes especially have been prepared, their DNA binding studied, and potential relevance to cytotoxicity examined. This chapter focuses on how DNA structure and reactivity is modulated through interactions with PPCs with emphasis on novel aspects of such structure and reactivity. How these major changes are further reflected in damaged DNA-protein binding and cellular effects are reviewed. We further review, for the first time, the great structural diversity achieved in PPC complex design and summarize their major DNA binding effects.
Abstract
Polynuclear platinum complexes (PPCs) represent a discrete structural class of DNA-binding agents with excellent antitumor properties. The use of at least two platinum coordinating units automatically means that multifunctional DNA binding modes are possible. The structural variability inherent in a polynuclear platinum structure can be harnessed to produce discrete modes of DNA binding, with conformational changes distinct from and indeed inaccessible to, the mononuclear agents such as cisplatin. Since our original contributions in this field a wide variety of dinuclear complexes especially have been prepared, their DNA binding studied, and potential relevance to cytotoxicity examined. This chapter focuses on how DNA structure and reactivity is modulated through interactions with PPCs with emphasis on novel aspects of such structure and reactivity. How these major changes are further reflected in damaged DNA-protein binding and cellular effects are reviewed. We further review, for the first time, the great structural diversity achieved in PPC complex design and summarize their major DNA binding effects.
Kapitel in diesem Buch
- Frontmatter i
- About the Editors v
- Historical Development and Perspectives of the Series vii
- Preface to Volume 18 ix
- Contents xiii
- Contributors to Volume 18 xix
- Titles of Volumes 1–44 in the Metal Ions in Biological Systems Series xxiii
- Contents of Volumes in the Metal Ions in Life Sciences Series xxv
- 1. CISPLATIN AND OXALIPLATIN: OUR CURRENT UNDERSTANDING OF THEIR ACTIONS 1
- 2. POLYNUCLEAR PLATINUM COMPLEXES. STRUCTURAL DIVERSITY AND DNA BINDING 43
- 3. PLATINUM(IV) PRODRUGS 69
- 4. METALLOGLYCOMICS 109
- 5. THE DECEPTIVELY SIMILAR RUTHENIUM(III) DRUG CANDIDATES KP1019 AND NAMI-A HAVE DIFFERENT ACTIONS. WHAT DID WE LEARN IN THE PAST 30 YEARS? 141
- 6. MULTINUCLEAR ORGANOMETALLIC RUTHENIUM-ARENE COMPLEXES FOR CANCER THERAPY 171
- 7. MEDICINAL CHEMISTRY OF GOLD ANTICANCER METALLODRUGS 199
- 8. COORDINATION COMPLEXES OF TITANIUM(IV) FOR ANTICANCER THERAPY 219
- 9. HEALTH BENEFITS OF VANADIUM AND ITS POTENTIAL AS AN ANTICANCER AGENT 251
- 10. GALLIUM COMPLEXES AS ANTICANCER DRUGS 281
- 11. NON-COVALENT METALLO-DRUGS: USING SHAPE TO TARGET DNA AND RNA JUNCTIONS AND OTHER NUCLEIC ACID STRUCTURES 303
- 12. NUCLEIC ACID QUADRUPLEXES AND METALLO-DRUGS 325
- 13. ANTITUMOR METALLODRUGS THAT TARGET PROTEINS 351
- 14. METALLOINTERCALATORS AND METALLOINSERTORS: STRUCTURAL REQUIREMENTS FOR DNA RECOGNITION AND ANTICANCER ACTIVITY 387
- 15. IRON AND ITS ROLE IN CANCER DEFENSE: A DOUBLE-EDGED SWORD 437
- 16. COPPER COMPLEXES IN CANCER THERAPY 469
- 17. TARGETING ZINC(II) SIGNALLING TO PREVENT CANCER 507
- SUBJECT INDEX 531
Kapitel in diesem Buch
- Frontmatter i
- About the Editors v
- Historical Development and Perspectives of the Series vii
- Preface to Volume 18 ix
- Contents xiii
- Contributors to Volume 18 xix
- Titles of Volumes 1–44 in the Metal Ions in Biological Systems Series xxiii
- Contents of Volumes in the Metal Ions in Life Sciences Series xxv
- 1. CISPLATIN AND OXALIPLATIN: OUR CURRENT UNDERSTANDING OF THEIR ACTIONS 1
- 2. POLYNUCLEAR PLATINUM COMPLEXES. STRUCTURAL DIVERSITY AND DNA BINDING 43
- 3. PLATINUM(IV) PRODRUGS 69
- 4. METALLOGLYCOMICS 109
- 5. THE DECEPTIVELY SIMILAR RUTHENIUM(III) DRUG CANDIDATES KP1019 AND NAMI-A HAVE DIFFERENT ACTIONS. WHAT DID WE LEARN IN THE PAST 30 YEARS? 141
- 6. MULTINUCLEAR ORGANOMETALLIC RUTHENIUM-ARENE COMPLEXES FOR CANCER THERAPY 171
- 7. MEDICINAL CHEMISTRY OF GOLD ANTICANCER METALLODRUGS 199
- 8. COORDINATION COMPLEXES OF TITANIUM(IV) FOR ANTICANCER THERAPY 219
- 9. HEALTH BENEFITS OF VANADIUM AND ITS POTENTIAL AS AN ANTICANCER AGENT 251
- 10. GALLIUM COMPLEXES AS ANTICANCER DRUGS 281
- 11. NON-COVALENT METALLO-DRUGS: USING SHAPE TO TARGET DNA AND RNA JUNCTIONS AND OTHER NUCLEIC ACID STRUCTURES 303
- 12. NUCLEIC ACID QUADRUPLEXES AND METALLO-DRUGS 325
- 13. ANTITUMOR METALLODRUGS THAT TARGET PROTEINS 351
- 14. METALLOINTERCALATORS AND METALLOINSERTORS: STRUCTURAL REQUIREMENTS FOR DNA RECOGNITION AND ANTICANCER ACTIVITY 387
- 15. IRON AND ITS ROLE IN CANCER DEFENSE: A DOUBLE-EDGED SWORD 437
- 16. COPPER COMPLEXES IN CANCER THERAPY 469
- 17. TARGETING ZINC(II) SIGNALLING TO PREVENT CANCER 507
- SUBJECT INDEX 531
