LEADER 04481nam 22005415 450 001 9910298586003321 005 20200706175932.0 010 $a981-10-6547-0 024 7 $a10.1007/978-981-10-6547-7 035 $a(CKB)4100000000587613 035 $a(DE-He213)978-981-10-6547-7 035 $a(MiAaPQ)EBC5050085 035 $a(PPN)204531365 035 $a(EXLCZ)994100000000587613 100 $a20170919d2018 u| 0 101 0 $aeng 135 $aurnn|008mamaa 181 $ctxt$2rdacontent 182 $cc$2rdamedia 183 $acr$2rdacarrier 200 10$aAdvancing Development of Synthetic Gene Regulators $eWith the Power of High-Throughput Sequencing in Chemical Biology /$fby Anandhakumar Chandran 205 $a1st ed. 2018. 210 1$aSingapore :$cSpringer Singapore :$cImprint: Springer,$d2018. 215 $a1 online resource (XV, 114 p. 49 illus., 44 illus. in color.) 225 1 $aSpringer Theses, Recognizing Outstanding Ph.D. Research,$x2190-5053 311 $a981-10-6546-2 320 $aIncludes bibliographical references. 327 $aOverview of Next-Generation Sequencing Technologies and its application in Chemical Biology -- Next Generation Sequencing Studies Guide the Design of Pyrrole-Imidazole Polyamides with Improved Binding Specificity by the Addition of ?-alanine -- Genome-Wide Assessment of the Binding Effects of Artificial Transcriptional Activators by Utilizing the Power of High-Throughput Sequencing -- Deciphering the genomic targets of alkylating polyamide conjugates using high-throughput sequencing. 330 $aThis book focuses on an ?outside the box? notion by utilizing the powerful applications of next-generation sequencing (NGS) technologies in the interface of chemistry and biology. In personalized medicine, developing small molecules targeting a specific genomic sequence is an attractive goal. N-methylpyrrole (P)?N-methylimidazole (I) polyamides (PIPs) are a class of small molecule that can bind to the DNA minor groove. First, a cost-effective NGS (ion torrent platform)-based Bind-n-Seq was developed to identify the binding specificity of PIP conjugates in a randomized DNA library. Their biological influences rely primarily on selective DNA binding affinity, so it is important to analyze their genome-wide binding preferences. However, it is demanding to enrich specifically the small-molecule-bound DNA without chemical cross-linking or covalent binding in chromatinized genomes. Herein is described a method that was developed using high-throughput sequencing to map the differential binding sites and relative enriched regions of non-cross-linked SAHA-PIPs throughout the complex human genome. SAHA-PIPs binding motifs were identified and the genome-level mapping of SAHA-PIPs-enriched regions provided evidence for the differential activation of the gene network. A method using high-throughput sequencing to map the binding sites and relative enriched regions of alkylating PIP throughout the human genome was also developed. The genome-level mapping of alkylating the PIP-enriched region and the binding sites on the human genome identifies significant genomic targets of breast cancer. It is anticipated that this pioneering low-cost, high through-put investigation at the sequence-specific level will be helpful in understanding the binding specificity of various DNA-binding small molecules, which in turn will be beneficial for the development of small-molecule-based drugs targeting a genome-level sequence. . 410 0$aSpringer Theses, Recognizing Outstanding Ph.D. Research,$x2190-5053 606 $aBiotechnology 606 $aGene therapy 606 $aBioorganic chemistry 606 $aBiotechnology$3https://scigraph.springernature.com/ontologies/product-market-codes/C12002 606 $aGene Therapy$3https://scigraph.springernature.com/ontologies/product-market-codes/B12020 606 $aBioorganic Chemistry$3https://scigraph.springernature.com/ontologies/product-market-codes/C19010 615 0$aBiotechnology. 615 0$aGene therapy. 615 0$aBioorganic chemistry. 615 14$aBiotechnology. 615 24$aGene Therapy. 615 24$aBioorganic Chemistry. 676 $a660.6 700 $aChandran$b Anandhakumar$4aut$4http://id.loc.gov/vocabulary/relators/aut$0768466 906 $aBOOK 912 $a9910298586003321 996 $aAdvancing Development of Synthetic Gene Regulators$91565444 997 $aUNINA