Advancing Development of Synthetic Gene Regulators

With the Power of High-Throughput Sequencing in Chemical Biology

Anandhakumar Chandran (Autor)

Buch | Softcover

114 Seiten

2019 | Softcover reprint of the original 1st ed. 2018
Springer Verlag, Singapore
978-981-13-4899-0 (ISBN)

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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.

Overview 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 β-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.

Erscheinungsdatum	20.12.2018
Reihe/Serie	Springer Theses
Zusatzinfo	44 Illustrations, color; 5 Illustrations, black and white; XV, 114 p. 49 illus., 44 illus. in color.
Verlagsort	Singapore
Sprache	englisch
Maße	155 x 235 mm
Themenwelt	Medizin / Pharmazie ► Medizinische Fachgebiete ► Biomedizin
	Studium ► 2. Studienabschnitt (Klinik) ► Humangenetik
	Naturwissenschaften ► Biologie ► Biochemie
	Naturwissenschaften ► Biologie ► Genetik / Molekularbiologie
	Naturwissenschaften ► Chemie ► Organische Chemie
	Technik ► Umwelttechnik / Biotechnologie
Schlagworte	Bind-n-Seq • High-throughput sequencing • Next generation sequencing • PIP • small molecules targeting specific genomic sequence
ISBN-10	981-13-4899-5 / 9811348995
ISBN-13	978-981-13-4899-0 / 9789811348990
Zustand	Neuware