Advancing development of synthetic gene regulators : with the power of high-throughput sequencing in chemical biology / Anandhakumar Chandran.
Chandran, Anandhakumar, author.
2018
QH450
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Title
Advancing development of synthetic gene regulators : with the power of high-throughput sequencing in chemical biology / Anandhakumar Chandran.
Author
Chandran, Anandhakumar, author.
ISBN
9789811065477 (electronic book)
9811065470 (electronic book)
9789811065460
9811065462
DOI
https://doi.org/10.1007/978-981-10-6547-7
Published
Singapore : Springer, [2018].
Language
English
Description
1 online resource (xv, 114 pages) : illustrations.
Item Number
10.1007/978-981-10-6547-7 doi
Call Number
QH450
Dewey Decimal Classification
572.8/65
Summary
This book focuses on an “outside the box” notion by utilizing the powerful applications of next-generation sequencing (NGS) technologies in the interface of chemistry and biology. In personalized medicine, developing small molecules targeting a specific genomic sequence is an attractive goal. N-methylpyrrole (P)–N-methylimidazole (I) polyamides (PIPs) are a class of small molecule that can bind to the DNA minor groove. First, a cost-effective NGS (ion torrent platform)-based Bind-n-Seq was developed to identify the binding specificity of PIP conjugates in a randomized DNA library. Their biological influences rely primarily on selective DNA binding affinity, so it is important to analyze their genome-wide binding preferences. However, it is demanding to enrich specifically the small-molecule-bound DNA without chemical cross-linking or covalent binding in chromatinized genomes. Herein is described a method that was developed using high-throughput sequencing to map the differential binding sites and relative enriched regions of non-cross-linked SAHA-PIPs throughout the complex human genome. SAHA-PIPs binding motifs were identified and the genome-level mapping of SAHA-PIPs-enriched regions provided evidence for the differential activation of the gene network. A method using high-throughput sequencing to map the binding sites and relative enriched regions of alkylating PIP throughout the human genome was also developed. The genome-level mapping of alkylating the PIP-enriched region and the binding sites on the human genome identifies significant genomic targets of breast cancer. It is anticipated that this pioneering low-cost, high through-put investigation at the sequence-specific level will be helpful in understanding the binding specificity of various DNA-binding small molecules, which in turn will be beneficial for the development of small-molecule-based drugs targeting a genome-level sequence.
Note
"Doctoral thesis accepted by Kyoto University, Kyoto, Japan."
Bibliography, etc. Note
Includes bibliographical references.
Access Note
Access limited to authorized users.
Digital File Characteristics
text file PDF
Source of Description
Online resource; title from PDF title page (SpringerLink, viewed October 3, 2017).
Series
Springer theses.
Available in Other Form
Print version: 9789811065460
Linked Resources
Online Access
Record Appears in
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Supervisor's Foreword; Part of this Thesis have been Published in the Following Journal Articles:Chandran A, Syed J, Li Y, Sato S, Bando T, Sugiyama H (2016) "Genome-Wide Assessment of the Binding Effects of Artificial Transcriptional Activators by High-Throughput Sequencing." Chembiochem 17:1905-1910. doi: 10.1002/cbic.201600274.Chandran A, Syed J, Taylor RD, Kashiwazaki G, Sato S, Hashiya K, Bando T, Sugiyama H (2016) "Deciphering the genomic targets of alkylating polyamide conjugates using high-throughput sequencin; Acknowledgements; Contents

1 Overview of Next-Generation Sequencing Technologies and Its Application in Chemical BiologyAbstract; 1.1 General Introduction: Next Generation Sequencing (NGS) Principles and Platforms; 1.1.1 Sequencing by Synthesis (SBS); 1.1.1.1 Illumina; 1.1.1.2 Roche 454; 1.1.1.3 Ion Torrent; 1.1.2 Single-Molecule Sequencing (SMS); 1.1.2.1 Helicos; 1.1.2.2 Pacific Biosciences (PacBio); 1.1.3 Sequencing by Ligation (SBL); 1.1.3.1 Polonator and SOLiD (Support Oligonucleotide Ligation Detection); 1.2 Applications of NGS in Chemical Biology; 1.2.1 Genome-Wide Localization of Non-B DNA Using Small Molecules

1.2.2 Decoding of DNA Base Modification in Single Molecule Level1.2.2.1 Studies Targets Epigenetically Modified Bases; 1.2.2.2 DNA Strand Breakage and Damaged Bases; 1.2.3 Aptamer Selection Using Massively Parallel Sequencing; 1.3 Development of N-Methylpyrrole (P)-N-Methylimidazole (I) Polyamides (PIP) and Its Conjugates; 1.4 PIP Based Gene Regulation; 1.5 Utilization of NGS in PIP Based Small Molecule Studies; 1.5.1 Guiding the Design and Screening of Small Molecule Using NGS; 1.5.2 Analysis of Gene Expression Induced by PIP Based Small Molecules; 1.5.2.1 Transcriptome Studies

2.3.1.1 General Scheme for Synthesis of Biotin-Conjugated Polyamides2.3.2 Oligomer Sequences Used in Bind-n-Seq Method; 2.3.3 Bind-n-Seq; 2.3.4 Surface Plasmon Resonance (SPR); 2.3.4.1 General Scheme for Synthesis of Polyamides Used for SPR Analysis; 2.3.4.2 SPR Analysis; References; 3 Genome-Wide Assessment of the Binding Effects of Artificial Transcriptional Activators by Utilizing the Power of High-Throughput Sequencing; Abstract; 3.1 Introduction; 3.2 Results and Discussion; 3.2.1 Revealing the Unique Gene Set Activation Mechanism of PIP Conjugates in the Human Genome

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