Résumé
The human telomeric i-motif (htel-iM) is a unique higher-order DNA structure formed by the cytosine-rich (C) sequences at the end of human telomeres. Studies have shown that htel-iM plays a significant role in the transcriptional regulation of telomeric repeat-containing RNA (TERRA) ‚ maintenance of telomere function and inhibition of telomerase activity. Thus‚ it is closely related to the development and progression of many cancers and is a promising new target for cancer treatment therapy. Compared to other nucleic acid higher-order structures such as G-quadruplexes‚ the stability of htel-iM is much weaker and affected by many factors like buffer pH‚ ionic conditions and molecular crowding environments. Therefore the existence of the iM structures in near neutral physiological conditions has been uncertain for a long time. Recently‚ using in-vitro screened small molecule ligands to selectively recognize and stabilize htel-iM provides a new strategy for the exploration of the biological relevance of htel-iM. Thus it has become a research hotspot to take telomere as a cancer treatment target. However‚ so far the reported small molecule ligands selectively targeting the htel-iM are far from sufficient compared with those targeting other higher-order nucleic acid structures. In this review‚ the discovery and the characteristic of the iM structures are briefly described‚ with an emphasis on the in-vitro affecting factors of the htel-iM structure‚ the reported htel-iM ligands and its biological relevance and regulation mechanisms‚ which will be helpful in further exploration of the htel-iM structure and ligand screening in near physiological conditions‚ and understanding the mechanism and developing novel therapeutic strategies for cancer treatment targeting the htel-iM structures.
Résumé
Objective To establish a method that can accurately and efficiently screen potential pharmaceutical agents targeting Nuclear Receptor Retinoid X receptor-α (RXRα) from Traditional Chinese Medicine .Methods Based on the principle of Receptor-Ligand Recognition ,the fusion protein of His-RXRαLBD and the active fractions were mixed to incubate for capturing and identif-ying potential ligand of RXRα,and then the identified ligand was evaluated for RXRα-dependent anti-inflammation effect .Results Baohuoside Ⅰ from Epimedium brevicornum Maxim .was identified as a RXRα binder ,and could induce RXRα-dependent anti-in-flammation effect .Conclusion The method was an efficient strategy to accurately identify active compounds from natural products , to expedite the discovery of natural RXRαregulator ,and also to share the thought with other receptors in identifying ligand .