Investigating the Intramolecular Competition of Different RNA Binding Motifs for Neomycin B by Native Top-Down Mass Spectrometry.
Chempluschem
; 89(8): e202400178, 2024 Aug.
Article
in En
| MEDLINE
| ID: mdl-38758051
ABSTRACT
The ongoing search for small molecule drugs that target ribonucleic acids (RNA) is complicated by a limited understanding of the principles that govern RNA-small molecule interactions. Here we have used stoichiometry-resolved native top-down mass spectrometry (MS) to study the binding of neomycin B to small model hairpin RNAs, an unstructured RNA, and a viral RNA construct. For 15-22â
nt model RNAs with hairpin structure, we found that neomycin B binding to hairpin loops relies on interactions with both the nucleobases and the 2'-OH groups, and that a simple 5' or 3' overhang can introduce an additional binding motif. For a 47â
nt RNA construct derived from stem IA of the human immunodeficiency virus 1 (HIV-1) rev response element (RRE) RNA, native top-down MS identified four different binding motifs, of which the purine-rich internal loop showed the highest affinity for neomycin B. Stoichiometry-resolved binding site mapping by native top-down MS allows for a new perspective on binding specificity, and has the potential to reveal unexpected principles of small molecule binding to RNA.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Mass Spectrometry
/
Framycetin
Language:
En
Journal:
Chempluschem
Year:
2024
Document type:
Article
Affiliation country:
Austria
Country of publication:
Alemania