Quadruplex-Forming Motif Inserted into 3 ' UTR of Ty1his3-AI Retrotransposon Inhibits Retrotransposition in Yeast

0542265 - BFÚ 2022 RIV CH eng J - Journal Article
Tokan, Viktor - Lorenzo, Jose Luis Rodriguez - Jedlička, Pavel - Kejnovská, Iva - Hobza, Roman - Kejnovský, Eduard
Quadruplex-Forming Motif Inserted into 3 ' UTR of Ty1his3-AI Retrotransposon Inhibits Retrotransposition in Yeast.
Biology. Roč. 10, č. 4 (2021), č. článku 347. E-ISSN 2079-7737
R&D Projects: GA ČR(CZ) GA18-00258S; GA ČR(CZ) GA21-00580S
Institutional support: RVO:68081707
Keywords : Ty1 LTR retrotransposon * G-quadruplex * retrotransposition * N-methyl mesoporphyrin (NMM) * Pif1 helicase * yeast
OECD category: Other biological topics
Impact factor: 5.168, year: 2021
Method of publishing: Open access
https://www.mdpi.com/2079-7737/10/4/347

Current multiagent chemotherapy regimens have improved the cure rate in acute leukemia patients, but they are highly toxic and poorly efficient in relapsed patients. To improve the treatment approaches, new specific molecules are needed. The G-quadruplexes (G4s), which are noncanonical nucleic acid structures found in specific guanine-rich DNA or RNA, are involved in many cellular events, including control of gene expression. G4s are considered as targets for the development of anticancer agents. Heterocyclic molecules are well known to target and stabilize G4 structures. Thus, a new series of 2,9-bis[(substituted-aminomethyl)phenyl]-1,10-phenanthroline derivatives (1a-i) was designed, synthesized, and evaluated against five human myeloid leukemia cell lines (K562, KU812, MV4-11, HL60, and U937). Their ability to stabilize various oncogene promoter G4 structures (c-MYC, BCL-2, and K-RAS) as well as the telomeric G4 was also determined through the fluorescence resonance energy transfer melting assay and native mass spectrometry. In addition, the more bioactive ligands 1g-i were tested for telomerase activity in HuT78 and MV4-11 protein extracts.
Permanent Link: http://hdl.handle.net/11104/0319724