title: Fluorescent 2-Aminopyridine Nucleobases for Triplex-Forming Peptide Nucleic Acids.
abstract: Development of new fluorescent peptide nucleic acids (PNAs) is important for fundamental research and practical applications. The goal of this study was the design of fluorogenic nucleobases for incorporation in triplex-forming PNAs. The underlying design principle was the use of a protonation event that accompanied binding of a 2-aminopyridine (M) nucleobase to a G-C base pair as an on switch for a fluorescence signal. Two fluorogenic nucleobases, 3-(1-phenylethynyl)-M and phenylpyrrolo-M, were designed, synthesized and studied. The new M derivatives provided modest enhancement of fluorescence upon protonation but showed reduced RNA binding affinity and quenching of fluorescence signal upon triple-helix formation with cognate double-stranded RNA. Our study illustrates the principal challenges of design and provides guidelines for future improvement of fluorogenic PNA nucleobases. The 3-(1-phenylethynyl)-M may be used as a fluorescent nucleobase to study PNA-RNA triple-helix formation.
authors.affiliation: Department of Chemistry, Binghamton University, The State University of New York, Binghamton, NY, 13902, USA.
authors.forename: Samwel K
authors.initials: SK
authors.lastname: Cheruiyot
authors.affiliation: Department of Chemistry, Binghamton University, The State University of New York, Binghamton, NY, 13902, USA. erozners@binghamton.edu.
authors.forename: Eriks
authors.initials: E
authors.lastname: Rozners
mesh_terms: D000631:Aminopyridines / Q000737:chemistry*; D005453:Fluorescence; D015394:Molecular Structure; D020135:Peptide Nucleic Acids / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000631:Aminopyridines; D020135:Peptide Nucleic Acids; C032439:alpha-aminopyridine
keywords: double-stranded RNA; fluorogenic nucleobase; peptide nucleic acids; triple helices