14. METALLOINTERCALATORS AND METALLOINSERTORS: STRUCTURAL REQUIREMENTS FOR DNA RECOGNITION AND ANTICANCER ACTIVITY
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Ulrich Schatzschneider
Abstract
As the carrier of the inheritable information in cells, DNA has been the target of metal complexes for over 40 years. In this chapter, the focus will be on non-covalent recognition of the highly structured DNA surface by substitutionally inert metal complexes capable of either sliding in between the normal base pairs as metallointercalators or flipping out thermodynamically destabilized mispaired nucleobases as metalloinsertors. While most of the compounds discussed are based on ruthenium(II) and rhodium(III) due to their stable octahedral coordination environment and low-spin 4d6 electronic configuration, most recent developments of alternative metal complexes, based on both transition metals and main group elements, will also be highlighted. A particular focus of the coverage is on structural data from X-ray structure analysis, which now provides details of the interaction at unprecedented details and will enable development of novel DNA binding probes for fundamental studies as well as new anticancer drug candidates.
Abstract
As the carrier of the inheritable information in cells, DNA has been the target of metal complexes for over 40 years. In this chapter, the focus will be on non-covalent recognition of the highly structured DNA surface by substitutionally inert metal complexes capable of either sliding in between the normal base pairs as metallointercalators or flipping out thermodynamically destabilized mispaired nucleobases as metalloinsertors. While most of the compounds discussed are based on ruthenium(II) and rhodium(III) due to their stable octahedral coordination environment and low-spin 4d6 electronic configuration, most recent developments of alternative metal complexes, based on both transition metals and main group elements, will also be highlighted. A particular focus of the coverage is on structural data from X-ray structure analysis, which now provides details of the interaction at unprecedented details and will enable development of novel DNA binding probes for fundamental studies as well as new anticancer drug candidates.
Chapters in this book
- 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
Chapters in this book
- 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
