PDF(Pubmed)
Abstract：
Aberrant gene expression underlies numerous human ailments. Hence, developing small molecules to target and remedy dysfunctional gene regulation has been a long-standing goal at the interface of chemistry and medicine. A major challenge for designing small molecule therapeutics aimed at targeting desired genomic loci is the minimization of widescale disruption of genomic functions. To address this challenge, we rationally design polyamide-based multi-functional molecules, i.e., Synthetic Genome Readers/Regulators (SynGRs), which, by design, target distinct sequences in the genome. Herein, we briefly review how SynGRs access chromatin-bound and chromatin-free genomic sites, then highlight the methods for the study of chromatin processes using SynGRs on positioned nucleosomes in vitro or disease-causing repressive genomic loci in vivo.
摘要：
基因异常表达是许多人类疾病的基础。因此，开发小分子靶向和治疗功能失调的基因调节一直是化学和医学界面的长期目标。设计旨在靶向所需基因组基因座的小分子治疗剂的主要挑战是基因组功能的大规模破坏的最小化。为了应对这一挑战，我们合理设计聚酰胺基多功能分子，即，合成基因组读取器/调节剂（SynGR），which,通过设计,靶向基因组中不同的序列。在这里，我们简要回顾了SynGRs如何访问染色质结合和无染色质基因组位点，然后重点介绍了使用SynGR在体外定位的核小体或体内引起疾病的抑制性基因组基因座上研究染色质过程的方法。
