Abstract

6-Aminophenanthridine (6AP), a plant alkaloid possessing antiprion activity, inhibits ribosomal RNA dependent protein folding activity of the ribosome (referred as PFAR). We have compared 6AP and its three derivatives 6AP8CI, 6AP8CF(3) and 6APi for their activity in inhibition of PFAR. Since PFAR inhibition requires 6AP and its derivatives to bind to the ribosomal RNA (rRNA), we have measured the binding affinity of these molecules to domain V of 23S rRNA using fluorescence spectroscopy. Our results show that similar to the antiprion activity, both the inhibition of PFAR and the affinity towards rRNA follow the order 6AP8CF(3) > 6AP8Cl > 6AP, while 6APi is totally inactive. To have a molecular insight for the difference in activity despite similarities in structure, we have calculated the nucleus independent chemical shift using first principles density functional theory. The result suggests that the deviation of planarity in 6APi and steric hindrance from its bulky side chain are the probable reasons which prevent it from interacting with rRNA. Finally, we suggest a probable mode of action of 6AP, 6AP8CF(3) and 6AP8Cl towards rRNA. (C) 2013 Elsevier Masson SAS. All rights reserved.

Keywords

6AP; PFAR; Fluorescence; DFT; Ribosomal RNA

Published in

Biochimie
2013, Volume: 97, pages: 194-199

UKÄ Subject classification

Biochemistry and Molecular Biology
Other Biological Topics


Publication identifier

DOI: https://doi.org/10.1016/j.biochi.2013.10.012

Permanent link to this page (URI)

https://res.slu.se/id/publ/87066