title: An experimental and theoretical study of the gas-phase decomposition of monoprotonated peptide nucleic acids.
abstract: Peptide nucleic acids (PNAs) are DNA/RNA mimics which have recently generated considerable interest due to their potential use as antisense and antigene therapeutics and as diagnostic and molecular biology tools. These synthetic biomolecules were designed with improved properties over corresponding oligonucleotides such as greater binding affinity to complementary nucleic acids, enhanced cellular uptake, and greater stability in biological systems. Because of the stability and unique structure of PNAs, traditional sequence confirmation methods are not effective. Alternatively, electrospray ionization coupled with Fourier transform ion cyclotron resonance mass spectrometry shows great potential as a tool for the characterization and structural elucidation of these oligonucleotide analogs. Extensive gas-phase fragmentation studies of a mixed nucleobase 4-mer (AACT) and a mixed nucleobase 4-mer with an acetylated N-terminus (N-acetylated AACT) have been performed. Gas-phase collision-induced dissociation of PNAs resulted in water loss, cleavage of the methylene carbonyl linker containing a nucleobase, cleavage of the peptide bond, and the loss of nucleobases. These studies show that the fragmentation behavior of PNAs resembles that of both peptides and oligonucleotides. Molecular mechanics (MM+), semiempirical (AM1), and ab initio (STO-3G) calculations were used to investigate the site of protonation and determine potential low energy conformations. Computational methods were also employed to study prospective intramolecular interactions and provide insight into potential fragmentation mechanisms.
authors.affiliation: Department of Chemistry, Virginia Commonwealth University, Richmond 23284, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Flora
authors.forename: D D
authors.initials: DD
authors.lastname: Shillady
authors.forename: D C
authors.initials: DC
authors.lastname: Muddiman
mesh_terms: D000107:Acetylation; D017357:Cyclotrons; D005583:Fourier Analysis; D008401:Gas Chromatography-Mass Spectrometry; D008970:Molecular Weight; D020135:Peptide Nucleic Acids / Q000737:chemistry*; D011522:Protons; D009626:Terminology as Topic
chemical_list: D020135:Peptide Nucleic Acids; D011522:Protons