title: Probing a 2-aminobenzimidazole library for binding to RNA internal loops via two-dimensional combinatorial screening.
abstract: There are many potential RNA drug targets in bacterial, viral, and human transcriptomes. However, there are few small molecules that modulate RNA function. This is due, in part, to a lack of fundamental understanding about RNA-ligand interactions including the types of small molecules that bind to RNA structural elements and the RNA structural elements that bind to small molecules. In an effort to better understand RNA-ligand interactions, we diversified the 2-aminobenzimidazole core (2AB) and probed the resulting library for binding to a library of RNA internal loops. We chose the 2AB core for these studies because it is a privileged scaffold for binding RNA based on previous reports. These studies identified that N-methyl pyrrolidine, imidazole, and propylamine diversity elements at the R1 position increase binding to internal loops; variability at the R2 position is well tolerated. The preferred RNA loop space was also determined for five ligands using a statistical approach and identified trends that lead to selective recognition.
authors.affiliation: Department of Chemistry and the Center of Excellence in Bioinformatics and Life Sciences, The University at Buffalo, The State University of New York, 657 Natural Sciences Complex, Buffalo, New York 14260, United States.
authors.forename: Sai Pradeep
authors.initials: SP
authors.lastname: Velagapudi
authors.forename: Alexei
authors.initials: A
authors.lastname: Pushechnikov
authors.forename: Lucas P
authors.initials: LP
authors.lastname: Labuda
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: French
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Disney
mesh_terms: D001483:Base Sequence; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D006801:Humans; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D001562:Benzimidazoles; D054852:Small Molecule Libraries; D012313:RNA; C027391:2-aminobenzimidazole