@article{823674,
      recid = {823674},
      author = {Chandran, Anandhakumar,},
      title = {Advancing development of synthetic gene regulators : with  the power of high-throughput sequencing in chemical biology  /},
      pages = {1 online resource (xv, 114 pages) :},
      note = {"Doctoral thesis accepted by Kyoto University, Kyoto,  Japan."},
      abstract = {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.},
      url = {http://library.usi.edu/record/823674},
      doi = {https://doi.org/10.1007/978-981-10-6547-7},
}