2019

Nucleic Acids Research

Rocznik: 2019 | Tom: 47 | Numer: 20

artykuł naukowy

angielski

EN The trinucleotide repeat expansion disorders (TREDs) constitute of a group of >40 hereditary neurodegenerative human diseases associated with abnormal expansion of repeated sequences, such as CAG repeats. The pathogenic factor is a transcribed RNA or protein whose function in the cell is compromised. The disorders are progressive and incurable. Consequently, many ongoing studies are oriented at developing therapies. We have analyzed crystal structures of RNA containing CAG repeats in complex with synthetic cyclic mismatch-binding ligands (CMBLs). The models show well-defined interactions between the molecules in which the CMBLs mimic nucleobases as they form pseudo-canonical base pairs with adenosine residues and engage in extensive stacking interactions with neighboring nucleotides. The binding of ligands is associated with major structural changes of the CAG repeats, which is consistent with results of biochemical studies. The results constitute an early characterization of the first lead compounds in the search for therapy against TREDs. The crystallographic data indicate how the compounds could be further refined in future biomedical studies.

10906 - 10913

10.1093/nar/gkz832

http://academic.oup.com/nar/article-pdf/47/20/10906/31507485/gkz832.pdf

CC BY-NC-SA (uznanie autorstwa - użycie niekomercyjne - na tych samych warunkach)

ostateczna wersja opublikowana

09.2019

przed opublikowaniem

200

200