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BL
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| Record Number
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890966
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| Main Entry
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Kawamoto, Yusuke
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| Title & Author
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Synthesis and biological evaluation of pyrrole -- imidazole polyamide probes for visualization of telomeres /\ Yusuke Kawamoto.
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| Publication Statement
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Singapore :: Springer Nature :: Springer,, 2019.
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| Series Statement
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Springer theses
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| Page. NO
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1 online resource
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| ISBN
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9789811369124
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: 9811369127
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9789811369117
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9811369119
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| Notes
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"Doctoral thesis accepted by Kyoto University, Kyoto, Japan."
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| Bibliographies/Indexes
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Includes bibliographical references.
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| Contents
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Intro; Supervisor's Foreword; Parts of this thesis have been published in the following journal articles:; Acknowledgements; Contents; 1 Introduction: Sequence-Specific DNA Binding Pyrrole-Imidazole Polyamides and Their Applications; 1.1 Introduction; 1.2 Hairpin Structure and Pairing Rule of Py-Im Polyamides; 1.3 Varied Structures of Py-Im Polyamides; 1.4 Regulation of Gene Expression by Py-Im Polyamides; 1.5 Repression of Gene Expression by Sequence-Specific DNA Alkylation; 1.6 Transcriptional Activation; 1.7 Py-Im Polyamides for Imaging
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1.8 Other Functions and Applications of Py-Im Polyamides1.9 Conclusion and Outlook; 1.10 Scope of the Work; References; 2 Development of a New Method for Synthesis of Tandem Hairpin Pyrrole-Imidazole Polyamide Probes Targeting Human Telomeres; 2.1 Introduction; 2.2 Results and Discussion; 2.2.1 Synthesis of Conjugates 1-4; 2.2.2 UV-Visible Absorption Spectra and Fluorescence Spectra; 2.2.3 Binding Affinities and Specificities of Tandem Hairpin PI Polyamides; 2.3 Conclusion; 2.4 Supporting Information; 2.4.1 Materials for the Synthesis
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2.4.2 Materials for the Analysis of Spectra and Thermal Denaturation Analysis2.4.3 Synthetic Details of PI Polyamides; 2.4.4 Materials for Telomere Staining; 2.4.5 Telomeres Staining; References; 3 Tandem Trimer Pyrrole-Imidazole Polyamide Probes Targeting 18 Base Pairs in Human Telomere Sequences; 3.1 Introduction; 3.2 Results and Discussion; 3.2.1 Synthesis of Py-Im Polyamides; 3.2.2 Optical Characteristics of the Fluorescent Probes; 3.2.3 Binding Affinities to Match Sequence and Discrimination of Mismatch Sequences; 3.2.4 Human Telomere Staining with Two Py-Im Polyamide Probes
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3.3 Conclusion3.4 Supporting Information; 3.4.1 Materials; 3.4.2 Synthesis of Py-Im Polyamides; 3.4.3 Absorption and Fluorescence Spectra; 3.4.4 SPR Assays; 3.4.5 Telomeres Staining; References; 4 Targeting 24 bp Within Telomere Repeat Sequences with Tandem Tetramer Pyrrole-Imidazole Polyamide Probes; 4.1 Introduction; 4.2 Results and Discussion; 4.2.1 Synthesis of Py-Im Polyamides; 4.2.2 Comparative Analysis of Binding to Match Sequence; 4.2.3 Visualization of Human Telomeres to Compare Py-Im Polyamide Probes
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4.2.4 High-Throughput Sequencing of the Binding Sites of Py-Im Polyamide Probes for Telomeric Repeats4.3 Conclusion; 4.4 Supporting Information; 4.4.1 Materials; 4.4.2 Synthetic Details of Py-Im Polyamides; 4.4.3 SPR Assays; 4.4.4 Telomeres Staining and Calculation of S/B Ratios; 4.4.5 Identification of TDi59-A and TTet59-B Binding Sites in Genome; References; Curriculum Vitae
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| Abstract
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This book presents a novel method of synthesizing sequence-specific DNA binding pyrrole?imidazole (Py?Im) polyamides and demonstrates polyamides targeting longer base pairs than those previously reported and their cellular application. It discusses the development of the facile synthetic method of tandem hairpin Py?Im polyamides and the method of visualizing telomeres under mild conditions without harsh denaturation, as well as research resulting in the synthesis not only of previously reported tandem dimer polyamides but also longer tandem trimer and tetramer polyamides. Using fluorescently labeled tandem hairpin Py?Im polyamides targeting a human telomere repetitive sequence, the author successfully stained telomeres in fixed cells without denaturation. These fluorescently labeled tandem tetramer polyamides are able to visualize human telomeres with lower background signals than previous polyamide probes, suggesting that they have higher specificity for telomeres. As such, this book provides insights into recent advance in Py?Im polyamides, particularly the extension of the target sites and improvement of the specificity, which can be applied to the study of pyrrole?imidazole polyamides with higher sequence specificity and the function of telomeres.
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| Subject
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Imidazoles.
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Pyrroles.
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Imidazoles.
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| Subject
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Pyrroles.
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| Subject
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SCIENCE-- Chemistry-- Organic.
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| Dewey Classification
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547/.593
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| LC Classification
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QD401
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