التفاصيل البيبلوغرافية
| العنوان: |
In silico identification of novel ligands for G-quadruplex in the c- MYC promoter. |
| المؤلفون: |
Kang, Hyun-Jin, Park, Hyun-Ju1 hyunju85@skku.edu |
| المصدر: |
Journal of Computer-Aided Molecular Design. Apr2015, Vol. 29 Issue 4, p339-348. 10p. |
| مصطلحات موضوعية: |
*ONCOGENES, *GENETIC transcription, *DNA, *LIGANDS (Biochemistry), *MESSENGER RNA, *ANTINEOPLASTIC agents |
| مستخلص: |
G-quadruplex DNA formed in NHEIII region of oncogene promoter inhibits transcription of the genes. In this study, virtual screening combining pharmacophore-based search and structure-based docking screening was conducted to discover ligands binding to G-quadruplex in promoter region of c- MYC. Several hit ligands showed the selective PCR-arresting effects for oligonucleotide containing c- MYC G-quadruplex forming sequence. Among them, three hits selectively inhibited cell proliferation and decreased c- MYC mRNA level in Ramos cells, where NHEIII is included in translocated c- MYC gene for overexpression. Promoter assay using two kinds of constructs with wild-type and mutant sequences showed that interaction of these ligands with the G-quadruplex resulted in turning-off of the reporter gene. In conclusion, combined virtual screening methods were successfully used for discovery of selective c- MYC promoter G-quadruplex binders with anticancer activity. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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