Synthesis and Biological Evaluation of Pyrrole Imidazole Polyamide Probes for Visualization of Telomeres

This book presents a novel method of synthesizing sequence-specific DNA binding pyrroleimidazole (PyIm) 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 PyIm 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 PyIm 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 PyIm polyamides, particularly the extension of the target sites c

Nominated by Kyoto University as an outstanding Ph.D. thesis Includes a review chapter summarizing the history of and recent studies on PyIm Describes in detail the synthesis of PyIm polyamides using an automatic solid-phase peptide

Inhalt

1. General Introduction Sequence-specific DNA Binding PyrroleImidazole Polyamides and Their Applications.- 2. Development of a New Method for Synthesis of Tandem Hairpin PyrroleImidazole Polyamide Probes Targeting Human Telomeres.- 3. Tandem Trimer Pyrrole-Imidazole Polyamide Probes Targeting 18 Base Pairs in Human Telomere Sequences.- 4. Targeting 24 bp within Telomere Repeat Sequences with Tandem Tetramer PyrroleImidazole Polyamide Probes.