Comparative Conformational Studies Research Articles

Comparative conformational studies of 3,4,6-tri-O-acetyl-1,5-anhydro-2-deoxyhex-1-enitols at the DFT level

B3LYP and M06–2X optimization and MP2 single point calculations are reported for the 4H5 and 5H4 conformations of 3,4,6-tri-O-acetyl-D-allal, 3,4,6-tri-O-acetyl-D-galactal, 3,4,6-tri-O-acetyl-D-glucal, and 3,4,6-tri-O-acetyl-D-gulal. Significant discrepancies in predictions of relative energies and conformers' population for B3LYP and M06–2X optimized geometries are observed. Generally, B3LYP overestimates the conformers' energies with respect to MP2, whereas M06–2X slightly underestimates the conformers' energies. B3LYP failed to estimate the 4H5⇄5H4 conformational equilibrium for 3,4,6-tri-O-acetyl-D-galactal and 3,4,6-tri-O-acetyl-D-glucal. The M06–2X functional showed good agreement with experimental results for all glycals studied. The 4H5⇄5H4 conformational equilibrium for 3,4,6-tri-O-acetyl-D-allal and 3,4,6-tri-O-acetyl-D-gulal is governed by the vinylogous anomeric effect (VAE), whereas competition between the VAE and quasi 1,3-diaxial interactions influence this equilibrium for 3,4,6-tri-O-acetyl-D-galactal and 3,4,6-tri-O-acetyl-D-glucal. The orientation of the 4-OAc group influences the strength of the quasi 1,3-diaxial interactions between the 3-OAc and 5-CH2OAc groups. AIM analysis shows weak bonding interaction between the 3-OAc and 5-CH2OAc groups.

ChemInform Abstract: Synthesis of Tetrameric Branched RNA-DNA Conjugate and Branched-RNA Analogue and Their Comparative Conformational Studies by 500 MHz NMR Spectroscopy.

ChemInform Abstract: Synthesis of Tetrameric Branched RNA-DNA Conjugate and Branched-RNA Analogue and Their Comparative Conformational Studies by 500 MHz NMR Spectroscopy.

NMR and X-ray studies of isomeric 22,23-dihydroxy stigmastanes

A comparative conformational study of steroidal side chain of (22 R,23 R)- and (22 S,23 S)-dihydroxy stigmastane derivatives was performed using single crystal X-ray diffraction and NMR spectroscopy. The preferred conformation in solution was shown to be close to that in the crystal. (22 R,23 R)-Isomers typical for natural plant steroid hormones brassinosteroids adopt a conformation in which both hydroxyl groups are pointed toward unhindered α-side of the steroidal plane and can thus participate in biochemical processes. Unnatural (22 S,23 S)-counterparts exhibit a conformation with the two hydroxyl groups oriented in the opposite direction and sterically hindered by 21-methyl group and terminal side chain fragment.

Structure of isolated tyrosyl-glycyl-glycine tripeptide. A comparative conformational study with peptides containing an aromatic ring

Abstract The potential energy surface (PES) of tyrosyl-glycyl-glycine (YGG) tripeptide in solution was explored using EDMC (Electrostatically Driven Monte Carlo) and in the gas-phase by means of ab initio quantum chemical calculations. The theoretical computational analysis revealed that this tripeptide possesses a significant molecular flexibility. A C7 backbone conformation was the most energetically preferred for the central Gly residue, using both methodologies. Some new stable conformers that have not been previously reported were identified in the gas phase as well. This study points out the interplay of backbone and side-chain contributions in determining the relative stabilities of energy minima. In addition, the peptide backbone of YGG was compared with other small peptides containing aromatic side-chains (Phe-Gly-Gly and Trp-Gly-Gly). The comparison with experimental X-ray results was also satisfactory.

Influence of a lipid bilayer on the conformational behavior of amphotericin B derivatives — A molecular dynamics study

Amphotericin B (AmB) is an effective but very toxic antifungal antibiotic. In our laboratory a series of AmB derivatives of improved selectivity of action was synthesized and tested. To understand molecular basis of this improvement, comparative conformational studies of amphotericin B and its two more selective derivatives were carried out in an aqueous solution and in a lipid membrane. These molecular simulation studies revealed that within a membrane environment the conformational behavior of the derivatives differs significantly from the one observed for the parent molecule. Possible reasons for such a difference are analyzed. Furthermore, we hypothesize that the observed conformational transition within the polar head of AmB derivatives may lead to destabilization of antibiotic-induced transmembrane channels. Consequently, the selective toxicity of the derivatives should increase as ergosterol-rich liquid-ordered domains are more rigid and conformationally ordered than their cholesterol-containing counterparts, and as such may better support less stable channel structure.

Missing conformers. Comparative study of conformational cooling in cyanoacetic acid and methyl cyanoacetate isolated in low temperature inert gas matrixes

A comparative conformational study of two related systems, methyl cyanoacetate (MCA) and cyanoacetic acid (CAA), is presented. Ab initio calculations predicted that both systems have two nearly isoenergetic conformers separated by similar low energy barriers (about 3 kJ mol −1). In xenon matrixes deposited at temperatures above 40 K for MCA and above 20 K for CAA only one conformer was observed for each of the two systems. However, below those temperatures two MCA and two CAA conformers were trapped into the matrixes. Conformational cooling was found responsible for this behavior. Factors contributing to this effect are discussed.

Comparative conformational study of N-acetyl- N′-methylprolineamide with different basis sets

We report here the results on conformational free energies of N-acetyl- N′-methylprolineamide (Ac-Pro-NHMe) calculated using the ab initio and density functional methods with the reaction field theory at HF and B3LYP levels of theory with 6-31G(d,p) and 6-31+G(d) basis sets to investigate the effects of two different basis sets on the structure, cis– trans equilibrium, and rotational barrier of the proline dipeptide. There are no significant differences in the optimized structures for backbone and proline ring of Ac-Pro-NHMe at the HF level with 6-31G(d,p) and 6-31+G(d) basis sets. The relative electronic energies, enthalpies, and free energies with the 6-31+G(d) basis set are lower by 0.2–0.8 and 0.1–1.2 kcal/mol at HF and B3LYP levels than those with the 6-31G(d,p) basis set, respectively, which may be ascribed to the differences in the distribution of atomic charges. The HF/6-31+G(d) level has brought the unfavorable solvation by 0.1–1.5 kcal/mol in chloroform and water than the HF/6-31G(d,p) level, but there are small differences in dipole moments. The calculated cis populations and rotational barriers may indicate that the B3LYP/6-31+G(d)//HF/6-31+G(d) level combined by the frequency and solvation calculations at the HF/6-31+G(d) level appears to be the appropriate method in describing the cis– trans isomerization of the X-Pro peptide bond in solution.

Novel observations on thiophosphoryl-group transfer in sugar β-hydroxy phosphorodithioate systems. Synthesis and X-ray molecular structure of 1,6-anhydro-3,4-dideoxy-3,4-epithio-2-O-(p-tolylsulfonyl)-β-D-allopyranose

The reaction of 1,6;3,4-dianhydro-2-O-(p-tolylsulfonyl)-β-D-galactopyranose 6 with the triethylammonium salt of 2-mercapto-5,5-dimethyl-1,3,2-dioxaphosphorinane 2-sulfide 7′ gives the hitherto unknown 1,6-anhydro-3,4-dideoxy-3,4-epithio-2-O-(p-tolylsulfonyl)-β-D-allopyranose 8 in high yield. The intermediates in this reaction are: 1,6-anhydro-4-S-(5′, 5′-dimethyl-2′-thioxo-1′,3′,2′-dioxaphosphorinan-2′-yl)-4-thio-2-O-(p-tolylsulfonyl)-β-D-glucopyranose 9 and 1,6-anhydro-3-O-(5′, 5′-dimethyl-2′-thioxo-1′,3′,2′-dioxaphosphorinan-2′-yl)-4-thio-2-O-(p-tolylsulfonyl)-β-D-glucopyranose 10. The former can be obtained by addition of 2-mercapto-5,5-dimethyl-1,3,2-dioxaphosphorinane 2-sulfide 7 to the dianhydro sugar 6. Formation of the latter was confirmed by 31P NMR spectroscopy. Comparative conformational studies of dianhydro compound 6 and of episulfide 8 were undertaken. They revealed that, despite the opposite orientation of the epoxy and epithio groups, the overall conformation of 5- and 6-membered rings remains the same. The absolute configuration of compound 6 has been determined as 1R,2R,3S,4S,5R, and of compound 8 as 1R,2S,3S,4R,5R.

Synthesis of tetrameric branched RNA-DNA conjugate & branched-RNA analogue & their comparative conformational studies by 500 MHz NMR spectroscopy

We report herein the unambigous synthesis of pure tetrameric branched oligonucleotides A3′p5′G 2′p5′[dC] 3′p5′C ( 13) found naturally in gram-negative bacterium Stigmatella aurantiaca, and corresponding branched RNA analogue A3′p5′G 2′p5′C 3′p5′C ( 14). The conformational features of branched tetramers 13 and 14 have been elucidated and compared by assesing temperature- and concentration-dependent 1H and 31P chemical shifts, (C2′-exo and C3′-endo) and (C2′-endo, C3′-exo) equilibrium, and equilibrium amongst staggered γ and β rotamers using various 2D homo- and heteronuclear correlation, NOESY and ROESY experiments by 500 MHz NMR spectroscopy. Subsequently the conformational features of 13 and 14 have been compared with those of A 2′p5′G 3′p5′C (ref. 19) and U3′p5′A 2′p5′G 3′p5′C (ref. 24) found as the branch-point in the lariat formed in the pre-mRNA processing reaction (Splicing). These studies have clearly shown that (1) the intramolecular geometries of both 13 and 14 are dominated by stacking along the axis A3′→5′G2′→5′dC(C), but the RNA-DNA conjugate 13 has a more defined tertiary structure than that of 14, (2) these branched tetramers tend to associate intermolecularly above ∼2 mM concentration producing an aggregate which is vertically stacked along the axis A3′→5′G2′→5′dC(C), (3) the G2′→5′dC(C) stacking and the predominant S conformation of branch-point G found in 13 and 14 suggest that their structures are quite different from the ones found for U3′p5′A 2′p5′G 3′p5′C (ref. 24). Note however that the structures found for 13 and 14 are reminiscent of A2′→5′G stacking found in the branched trimer A 2′p5′G 3′p5′C (ref. 19).

Crystal and molecular structure of 2-[(hydroxyimino)(methylthio)methyl]-1-methylpyridinium chloride, C8H11N2OS+ Cl−

The X-ray structure analysis for single crystals of 2-[(hydroxyimino)(methylthio)methyl]-1-methylpyridinium chloride has been carried out, with finalR factor 0.029 in space groupP21/c. TheS-methyl substituted oxime group has theE configuration. The orientation of the oxime moiety in respect to the pyridinium, defined by N-C-C-N torsion angle, isgauche. The conformation of the title compound is similar to that of 2-[(hydroxyimino)(phenylthio)rnethyl]-1-methylpyridinium, but differs from that of 2-(hydroxyiminomethyl)-1-methylpyridinium which is highly active as the acetylcholinesterase reactivator. Molecular mechanics calculations and comparative conformational study of these three compounds suggest that the coplanarity of the oxime and pyridinium moieties is important for the antidotal activity in the nerve tissue, while the activity in blood does not seem to be related to the conformation observed in the crystalline state.

New features of the δ opioid receptor: Conformational properties of deltorphin I analogues

Deltorphin I is an opioid peptide of sequence H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH 2, recently isolated from the skin of Phyllomedusa bicolor. Its enormous selectivity towards the δ opioid receptor and the similarity of the conformation of the N-terminal part of the sequence with that of dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH 2), a μ selective peptide, prompted the synthesis, biological evaluation and comparative conformational study of four analogs. A 1H-NMR study showed that the conformational preferences of the N-terminal sequences of all peptides are similar. The different selectivities towards opioid receptors have been interpreted in terms of charge effects in the interaction with the membrane and at the receptor site and of hydrophobicity of the C-terminal part, when structured in a folded conformation.

Comparative conformational study of α and β epimers of 3-phenethyl-3-azabicyclo [3.2.1] octan-8-ol with atropine and azaprophen.

Conformational analysis of α(I) and β(II) epimers of 3-phenethyl-3-azabicyclo [3.2.1] octan-8-ol has been performed using the Molecular Mechanics Method (MM2). In both cases, the global minimum-energy conformer was the slight distorted chair form with the N-phenethyl group in equatorial position. The preferred conformation is in agreement with the form adopted in solid state and in solution in polar solvents. Higher energy differences between N-axial and N-equatorial conformations have been found with respect to tropine and 6-methyl-6-azabicyclo [3.2.1] octan-3-α-ol, the am i noalcohols components of atropine and azaprophen.

Conformational properties of deltorphin: New features of the δ-opioid receptor

Deltorphin is an opioid peptide with the sequence H-Tyr-D-Met-Phe-His-Leu-Met-Asp-NH 2, recently isolated from the skin of Phyllomedusa sauvagei. Its enormous selectivity towards the δ-opioid receptor and the similarity of the N-terminal part of the sequence with that of dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH 2), a μ selective peptide isolated from the same natural source, prompted a comparative conformational study. A 1H-NMR study in two different solvent systems showed that the conformational preferences of the N-terminal sequences of the two peptides are similar. The different selectivities towards opioid receptors have been interpreted in terms of charge effects. Besides a general trend consistent with the role of the membrane in the preselection of the peptides, the present study demonstrates the crucial role played by charged residues in the interaction inside the receptors.

Comparative conformational studies of polypeptides containing a high percentage of proline

Comparative conformational studies of polypeptides containing a high percentage of proline

A comparative conformational study of certain 2′-deoxy-2′-fluoro-arabinofuranosylcytosine nucleosides

The 270 MHz proton NMR spectra of 2′-deoxy-2′-fluoro-β- d-arabinofuranosyl-5-iodocytosine as well as the respective 5-bromo and 5-chloro derivatives have been iteratively analyzed using LAOCOON 3. The derived parameters indicate that the fluorine substituent in an arabino configuration results in an approx. 50 : 50 C(3′)- endo, C(2′)- endo conformer mixture. The C(4′)-C(5′) rotamer populations are 41% gg, 18% tg, and 41% gt. These equilibrium distributions, which are maintained within the series studied, are similar to that of other ara-C derivatives, but quite different from that of 2′-deoxycytidine. The agreement in chemical shift for each of the furanose protons within the series studied suggests a similar syn, anti distribution for each analog.

Comparative conformational studies of cyclic derivatives by13C NMR spectroscopy

The 13C chemical shift of the substituted or functionalized carbon of various medium and large rings is plotted against ring size (6–15 carbons). The curves thus obtained allow a conformational analysis of the corresponding derivatives.

Conformational studies of anthrax polypeptide, subtilis polypeptide, and synthetic poly- -L-glutamic acid.

AbstractPoly‐γ‐L‐glutamic acid has been synthesized by the activated pentachlorophenyl ester polymerization method and the molecule weight of the polymer was found to be 16,000. Comparative conformational studies on the synthetic and on the native polyglutamic acid mbtained from B. anthracis and B. subtilis were carried out using optical rotatory dispersion, circular dichroism, peptide absorption spectrum, and titration data. These results show that poly‐γ‐glutamic acid does not exhibit any conformational order under the conditions of investigation. At low degrees of ionization, restriction of conformational freedom via random “hypercoiling” of the chain appears likely.

Comparative conformational studies on the tryptic digestion fragments of human immunoglobulins M and G

IgM 1 immunoglobulins were cleaved into Fabμ and (Fc)5μ fragments by tryptic digestion. Comparative circular dichroism studies with the corresponding IgG fragments show that the Fab portions of IgG and IgM proteins have very similar CD spectral features, although the same is not true for their Fc fragments. These studies indicate the presence of higher amount of beta-structured regions in Fcμ than in Fcγ. Also, there are considerable differences in their pH-dependent structural transitions as measured by CD spectral changes. The conformational differences between IgG and IgM immunoglobulins are more pronounced in their Fc portions, which carry out class specific biological functions, rather than in Fab portions, which contain antigen combining sites.