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000823674 019__ $$a1004737070$$a1008870807$$a1011966535
000823674 020__ $$a9789811065477$$q(electronic book)
000823674 020__ $$a9811065470$$q(electronic book)
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000823674 0247_ $$a10.1007/978-981-10-6547-7$$2doi
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000823674 049__ $$aISEA
000823674 050_4 $$aQH450
000823674 08204 $$a572.8/65$$223
000823674 1001_ $$aChandran, Anandhakumar,$$eauthor.
000823674 24510 $$aAdvancing development of synthetic gene regulators :$$bwith the power of high-throughput sequencing in chemical biology /$$cAnandhakumar Chandran.
000823674 264_1 $$aSingapore :$$bSpringer,$$c[2018].
000823674 300__ $$a1 online resource (xv, 114 pages) :$$billustrations.
000823674 336__ $$atext$$btxt$$2rdacontent
000823674 337__ $$acomputer$$bc$$2rdamedia
000823674 338__ $$aonline resource$$bcr$$2rdacarrier
000823674 347__ $$atext file$$bPDF$$2rda
000823674 4901_ $$aSpringer theses
000823674 500__ $$a"Doctoral thesis accepted by Kyoto University, Kyoto, Japan."
000823674 504__ $$aIncludes bibliographical references.
000823674 5050_ $$aSupervisor's Foreword; Part of this Thesis have been Published in the Following Journal Articles:Chandran A, Syed J, Li Y, Sato S, Bando T, Sugiyama H (2016) "Genome-Wide Assessment of the Binding Effects of Artificial Transcriptional Activators by High-Throughput Sequencing." Chembiochem 17:1905-1910. doi: 10.1002/cbic.201600274.Chandran A, Syed J, Taylor RD, Kashiwazaki G, Sato S, Hashiya K, Bando T, Sugiyama H (2016) "Deciphering the genomic targets of alkylating polyamide conjugates using high-throughput sequencin; Acknowledgements; Contents
000823674 5058_ $$a1 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
000823674 5058_ $$a1.2.2 Decoding of DNA Base Modification in Single Molecule Level1.2.2.1 Studies Targets Epigenetically Modified Bases; 1.2.2.2 DNA Strand Breakage and Damaged Bases; 1.2.3 Aptamer Selection Using Massively Parallel Sequencing; 1.3 Development of N-Methylpyrrole (P)-N-Methylimidazole (I) Polyamides (PIP) and Its Conjugates; 1.4 PIP Based Gene Regulation; 1.5 Utilization of NGS in PIP Based Small Molecule Studies; 1.5.1 Guiding the Design and Screening of Small Molecule Using NGS; 1.5.2 Analysis of Gene Expression Induced by PIP Based Small Molecules; 1.5.2.1 Transcriptome Studies
000823674 5058_ $$a2.3.1.1 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
000823674 506__ $$aAccess limited to authorized users.
000823674 520__ $$aThis 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.
000823674 588__ $$aOnline resource; title from PDF title page (SpringerLink, viewed October 3, 2017).
000823674 650_0 $$aGenetic regulation.
000823674 77608 $$iPrint version: $$z9811065462$$z9789811065460$$w(OCoLC)1000599931
000823674 830_0 $$aSpringer theses.
000823674 852__ $$bebk
000823674 85640 $$3SpringerLink$$uhttps://univsouthin.idm.oclc.org/login?url=http://link.springer.com/10.1007/978-981-10-6547-7$$zOnline Access$$91397441.1
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000823674 980__ $$aBIB
000823674 982__ $$aEbook
000823674 983__ $$aOnline
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