Conformational Interconversion (conformational + interconversion)

Distribution by Scientific Domains


Selected Abstracts


Investigation of penetratin peptides Part 1.

JOURNAL OF PEPTIDE SCIENCE, Issue 4 2002
The environment dependent conformational properties of penetratin, two of its derivatives
Abstract The homeodomain, the DNA-binding domain of Antennapedia homeoprotein, is composed of three ,-helices and one ,-turn between helices II and III. Its third helix from the N -terminal (helix III) can translocate through the cell membrane into the nucleus and can be used as an intracellular vehicle for the delivery of oligopeptides and oligonucleotides. To the best of our knowledge, this helix III, called penetratin, which consists of 16 amino acids, is internalized by cells in a specific, non-receptor-mediated manner. For a better understanding of the mechanism of the transfer, the structure of penetratin was examined in both extracellular matrix-mimetic and membrane-mimetic environments; 1H-NMR and CD spectroscopic measurements were performed in mixtures of TFE/water with different ratios. The molecular conformations of two analogue peptides [(6,14-Phe)-penetratin and a 12 amino acid penetratin derivative (peptide 3)] were also studied. An atomic level comprehensive analysis of penetratin and its two analogues was performed. In a membrane-mimetic solvent system (TFEd2/water = 9 : 1), on the basis of 553 distance restraints, the 4,12 region of penetratin exhibits a bent, irregular helical structure on NMR examination. Interactions between hydrophobic amino acid residues in conjunction with H-bonds stabilize the secondary structure of the molecule. Thus, both derivatives adopt a helix-like conformation. However, while (6,14-Phe)-penetratin displays both ,-helical and 310 -helical features, the structure of peptide 3 is predominantly a 310 -helix. Of the three peptides, surprisingly (6,14-Phe)-penetratin has the largest helical content. An increase in the polarity of the molecular environment gradually disintegrates these helix-like secondary structures. In a highly aqueous molecular system (TFEd2/water = 1 : 9), the fast exchange of multiple conformers leads to too few distance restraints being extracted, therefore the NMR structures can no longer be determined. The NMR data show that only short-range order can be traced in these peptides. Under these conditions, the molecules adopt nascent helix-like structures. On the other hand, CD spectra could be recorded at any TFE/water ratio and the conformational interconversion could therefore be monitored as a function of the polarity of the molecular environment. The CD data were analysed comprehensively by the quantitative deconvolution method (CCA+). All three penetratin peptides display helical conformational features in a low dielectric medium, with significant differences as a function of their amino acid composition. However, these conformational features are gradually lost during the shift from an apolar to a polar molecular environment. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd. [source]


Computational study of the chair,chair interconversion and stereoelectronic interactions in 1,2,3-trithiacyclo-hexane (1,2,3-trithiane)

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 1 2004
Fillmore Freeman
Abstract Ab initio theory, density functional theory (DFT) and Møller,Plesset perturbation theory (MP2) with the 6,31G(d), 6,31++G(d), 6,31G(d,p), 6,31+G(d,p), 6,31++G(d,p), 6,311G(d,p) and 6,311+G(d,p) basis sets were used to study stereoelectronic hyperconjugative interactions and the mechanism of the chair,chair conformational interconversion in 1,2,3-trithiacyclohexane (1,2,3-trithiane). The relative energies, enthalpies, entropies, free energies and structural parameters of the chair, 1,4-twist and 2,5-twist conformers, a distorted 1,4-boat transition state and a 2,5-boat transition state were calculated. The HF calculated energy difference (,E) between the chair conformer of 1,2,3-trithiane and the distorted 1,4-boat transition state was 10.59,kcal,mol,1 (1 kcal=4.184,kJ). The 1,4-twist conformer and the 2,5-boat transition state are close in energy, as are the 2,5-twist conformer and the distorted 1,4-boat transition state. B3LYP/6,311+G(d,p) calculated the chair conformer of 1,2,3-trithiane to be 5.83, 10.09, and 5.96,kcal,mol,1, respectively, lower in energy than the 1,4-twist conformer, 2,5-twist conformer and 2,5-boat transition state. Intrinsic reaction coordinate (IRC) calculations were used to connect the transition state between the chair conformer and the 1,4-twist conformer. B3LYP/6,31+G(d,p) and B3LYP/6,311+G(d,p) calculated this transition state to be 14.25,kcal,mol,1 higher in energy than the chair conformer. In the chair conformer, the respective C4,H and C6,H bond lengths are equal, but the C5,Heq bond is longer than the C5,Hax bond. In the 1,4-twist conformer, the C4,Hiso bond lengths are equal, the C5,H,eq bond is longer than the C5,H,ax bond and the C6,H bond lengths are equal. In the 2,5-twist conformer, equal C,H bond lengths are found at C4 and at C5, but the C6,H,eq bond is longer than the C6,H,ax bond. Copyright © 2003 John Wiley & Sons, Ltd. Additional material for this paper is available in Wiley Intersciene [source]


A computational study of conformational interconversions in 1,4-dithiacyclohexane (1,4-dithiane)

JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 8 2003
Fillmore Freeman
Abstract Ab initio molecular orbital theory with the 6-31G(d), 6-31G(d,p), 6-31+G(d), 6-31+G(d,p), 6-31+G(2d,p), 6-311G(d), 6-311G(d,p), and 6-311+G(2d,p) basis sets and density functional theory (BLYP, B3LYP, B3P86, B3PW91) have been used to locate transition states involved in the conformational interconversions of 1,4-dithiacyclohexane (1,4-dithiane) and to calculate the geometry optimized structures, relative energies, enthalpies, entropies, and free energies of the chair and twist conformers. In the chair and 1,4-twist conformers the CHax and CHeq bond lengths are equal at each carbon, which suggest an absence of stereoelectronic hyperconjugative interactions involving carbon,hydrogen bonds. The 1,4-boat transition state structure was 9.53 to 10.5 kcal/mol higher in energy than the chair conformer and 4.75 to 5.82 kcal/mol higher in energy than the 1,4-twist conformer. Intrinsic reaction coordinate (IRC) calculations showed that the 1,4-boat transition state structure was the energy maximum in the interconversion of the enantiomers of the 1,4-twist conformer. The energy difference between the chair conformer and the 1,4-twist conformer was 4.85 kcal/mol and the chair-1,4-twist free energy difference (,G°c-t) was 4.93 kcal/mol at 298.15 K. Intrinsic reaction coordinate (IRC) calculations connected the transition state between the chair conformer and the 1,4-twist conformer. This transition state is 11.7 kcal/mol higher in energy than the chair conformer. The effects of basis sets on the 1,4-dithiane calculations and the relative energies of saturated and unsaturated six-membered dithianes and dioxanes are also discussed. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 909,919, 2003 [source]