Produktbild: Advancing Development of Synthetic Gene Regulators

Advancing Development of Synthetic Gene Regulators

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With the Power of High-Throughput Sequencing in Chemical Biology, Springer Theses

ISBN: 9811065462
ISBN 13: 9789811065460
Autor: Chandran, Anandhakumar
Verlag: Springer Verlag GmbH
Umfang: xv, 114 S., 5 s/w Illustr., 44 farbige Illustr., 114 p. 49 illus., 44 illus. in color.
Erscheinungsdatum: 28.09.2017
Auflage: 1/2018
Produktform: Gebunden/Hardback
Einband: Gebunden

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. 

Artikelnummer: 2736727 Kategorie:

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