Kobayashi Keita, Matsui Noriko, Usui Kenji
Faculty of Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, 7-1-20 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
J Nucleic Acids. 2011;2011:572873. doi: 10.4061/2011/572873. Epub 2011 Sep 6.
We demonstrated a method to screen for binders to a particular G-quadruplex sequence using easily designed short peptides consisting of naturally occurring amino acids and mining of binding data using statistical methods such as hierarchical clustering analysis (HCA). Despite the small size of the library used in this study, candidates of specific binders were identified. In addition, a selected peptide stabilized the G-quadruplex structure of a DNA oligonucleotide derived from the promoter region of the protooncogene c-MYC. This study illustrates how a peptide library can be designed and presents a screening guideline for construction of G-quadruplex binders. Such G-quadruplex peptide binders could be functionally modified to enable switching, cellular penetration, and organelle-targeting for cell and tissue engineering.
我们展示了一种方法,该方法使用由天然氨基酸组成的易于设计的短肽来筛选与特定G-四链体序列结合的分子,并使用层次聚类分析(HCA)等统计方法挖掘结合数据。尽管本研究中使用的文库规模较小,但仍鉴定出了特异性结合分子的候选物。此外,一种选定的肽稳定了源自原癌基因c-MYC启动子区域的DNA寡核苷酸的G-四链体结构。这项研究说明了如何设计肽文库,并为构建G-四链体结合分子提供了筛选指南。此类G-四链体肽结合分子可进行功能修饰,以实现用于细胞和组织工程的开关、细胞穿透及细胞器靶向功能。