Molecular dynamics and NMR studies of single-stranded PNAs

• Published in: Tetrahedron letters Vol. 35; no. 29; pp. 5105 - 5108
• Main Authors: Chen, Shiow-Meei, Mohan, Venkatraman, Kiely, John S, Griffith, Michael C., Griffey, Richard H.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 18.07.1994; Elsevier
• Subjects: Atomic and molecular physics; Calculations and mathematical techniques in atomic and molecular physics (excluding electron correlation calculations); Electronic structure of atoms, molecules and their ions: theory; Exact sciences and technology; Molecular properties and interactions with photons; Nuclear resonance and relaxation; Physics; Semi-empirical and empirical calculations (differential overlap, hückel, ppp methods, etc.); Hydrogen 1; Peptides; Overhauser effect; Molecular dynamics method; Theoretical study; Nucleic acids; NMR spectra; Experimental study; Rotational isomers; Organic compounds; Two dimension spectrometry
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/S0040-4039(00)77039-0

Proton NMR spectroscopy and molecular dynamics simulations are employed to investigate the conformations of PNA monomers, a dimer and an octamer. The monomers exist as a 70:30 mixture of two amide rotamers interconverting slowly on the NMR time scale at 20 °C. In the major form, the side chain carbonyl group points toward the glycine, which places the methylene protons in proximity to the 2-aminoethyl protons. The minor form places its side chain carbonyl group away from the glycine, and the methylene protons are close in space to the glycine α protons. The PNA CT-dimer has multiple rotamers at 20 °C. In contrast, a NOESY spectrum taken from an octamer indicates only a single conformer in solution at 40 °C. Single-stranded mono-, di- and octa-residue PNAs have been synthesized and studied via molecular dynamics and NMR. Conformational rotamers around the tertiary-amide bond are found and will be discussed.