Chemical Approaches to the Development of Artificial Transcription Factors Based on Pyrrole-Imidazole Polyamides.

Autor: Hidaka T; Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-Oiwakecho, Sakyo-ku, Kyoto, 606-8502, Japan., Sugiyama H; Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-Oiwakecho, Sakyo-ku, Kyoto, 606-8502, Japan.; Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida-Ushinomaecho, Sakyo-ku, Kyoto, 606-8501, Japan.
Jazyk: angličtina
Zdroj: Chemical record (New York, N.Y.) [Chem Rec] 2021 Jun; Vol. 21 (6), pp. 1374-1384. Date of Electronic Publication: 2020 Dec 17.
DOI: 10.1002/tcr.202000158
Abstrakt: To maintain the functions of living organisms, cells have developed complex gene regulatory networks. Transcription factors have a central role in spatiotemporal control of gene expression and this has motivated us to develop artificial transcription factors that mimic their function. We found that three functions could be mimicked by applying our chemical approaches: i) efficient delivery into organelles that contain target DNA, ii) specific DNA binding to the target genomic region, and iii) regulation of gene expression by interaction with other transcription coregulators. We chose pyrrole-imidazole polyamides (PIPs), sequence-selective DNA binding molecules, as DNA binding domains, and have achieved each of the required functions by introducing other functional moieties. The developed artificial transcription factors have potential as chemical tools that can be used to artificially modulate gene expression to enable cell fate control and to correct abnormal gene regulation for therapeutic purposes.
(© 2020 The Chemical Society of Japan & Wiley-VCH GmbH.)
Databáze: MEDLINE