Theoretical studies on the conformation of saccharides. IV. Solvent effect on the stability of β-maltose conformers

The conformational equilibria of four β-maltose conformers have been studied theoretically in 12 solvents. The stability of the conformers in dilute solution has been compared by using the continuum reaction field method. The solvation energy consists of electrostatic, dispersion, and cavity terms, which have been determined from the calculated properties of β-maltose and physicochemical properties of solvents. The calculated population of four conformers significantly depends on the solvent (e.g., in dioxane, M1:M2:M3:M4 = 53.3: 20.3:17.7:8.7; in dimethyl sulfoxide, 40.1:21.8:22.8:15.3; and in water, 25.7:17.5:26.3:30.5) and was found to correlate with experimentally observed data. The results obtained indicate that the conformation adopted by β-maltose in the crystalline form is not the one preferred in solution. The roles of the individual contributions to the solvation energy have been analyzed. Based on the determined abundance of conformers, averaged residual optical activity and vicinal carbon–proton coupling constants have been calculated and discussed from the point of view of the solution behavior of β-maltose.     

Solvent effect on the stability of mannobiose conformers

The conformational equilibria of seven methyl β-D -mannobioside conformers have been studied theoretically in five solvents. The structure of each individual conformer has been refined by the PCILO quantum-chemical method from the seven distinct low-energy regions determined from (Φ, Ψ) maps calculated by a potential function method. The stability of the conformers in dilute solution has been evaluated by using a method that consists of electrostatic, dispersion, and cavity terms. The calculated abundance of conformers depends on the solvent and results indicate that the preponderant conformer in the solution may not be the one adopted by mannobiose in the crystalline form. Based on the determined abundance of conformers, thermodynamically averaged nmr parameters, dipole moment, and linkage rotation have been calculated. The solvation behavior of methyl β-D -mannobioside is compared to those previously estimated for cellobiose and maltose.     

Experimental investigations on the backbone folding of proline-containing model tripeptides

Some proline-containing tripeptides with the general formulas R⁰CO-L -Pro-X-NHR³ (X = Gly,Sar,L -Ala,D -Ala) and R⁰CO-X-L -Pro-NHR³ (X = Gly,L -Ala,D -Ala) have been investigated in solution by ir and ¹H-nmr spectroscopies. Their favored conformational states depend mainly on both the primary structure and the chiral sequence of the molecules. In inert solvents the βII-folding mode is the most favored conformation for the L -Pro-D -Ala and L -Pro-Gly tripeptides, while the βII′-turn is largely preferred by D -Ala-L -Pro derivatives. Under the same conditions only about one-third of the whole conformers of L -Pro-L -Ala molecules adopts the βI-folding mode. Semiopened C₇C₅ and C₅C₇ conformations are appreciably populated in the L -Pro-L -Ala sequence, on the one hand, and in the Gly-L -Pro and L -Ala-L -Pro derivatives, on the other hand. In L -Pro-Sar and X-L -Pro models, the cis–trans isomerism around the middle tertiary amide function is observed. Thus cis L -Pro-Sar and L -Ala-L -Pro conformers are folded by an intramolecular i + 3 → i hydrogen bond, whereas cis D -Ala-L -Pro and Gly-L -Pro molecules accommodate an open conformation. In dimethylsulfoxide the βII- and βII′-folding modes are not essentially destabilized, as contrasted with the βI conformation, which is less populated. In water solution all the above-mentioned conformations, with the possible exception of the βII′-folding mode for D -Ala-L -Pro molecules, seem to vanish. Solute conformations are also compared with the crystal structures of four proline-containing tripeptides.     

The effect of β‐methylation on the conformation of α, β‐dehydrophenylalanine: a DFT study

Dehydroamino acids are non‐coded amino acids that offer unique conformational properties. Dehydrophenylalanine (ΔPhe) is most commonly used to modify bioactive peptides to constrain the topography of the phenyl ring in the side chain, which commonly serves as a pharmacophore. The Ramachandran maps (in the gas phase and in CHCl₃ mimicking environments) of ΔPhe analogues with methyl groups at the β position of the side chain as well as at the C‐terminal amide were calculated using the B3LYP/6‐31 + G** method. Unexpectedly, β‐methylation alone results in an increase of conformational freedom of the affected ΔPhe residue. However, further modification by introducing an additional methyl group at C‐terminal methyl amide results in a steric crowding that fixes the torsion angle ψ of all conformers to the value 123°, regardless of the Z or E position of the phenyl ring. The number of conformers is reduced and the accessible conformational space of the residues is very limited. In particular, (Z)‐Δ(βMe)Phe with the tertiary C‐terminal amide can be classified as the amino acid derivative that has a single conformational state as it seems to adopt only the β conformation. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.     

Theoretical studies on the conformation of saccharides. XIV. Structure and conformational properties of the glycosylamines

The 2-methylaminotetrahydropyran was used as a model to study conformational properties of the N-glycosidic linkage in glycosylamines. Relaxed two-dimensional conformational (phi, psi) maps in 20 solvents were calculated by a method in which the total energy is divided into the energy of the isolated molecule and the solvation energy. Molecular geometry optimization has been carried out for each conformer using the quantum chemical method PCILO. The calculated variations of the geometry are consistent with the results obtained by the statistical analysis of available experimental data retrieved from the Cambridge Structural Database. The calculated abundances of conformers show that the polarity of the solvent has little effect on the anomeric ratio, and the form having the methylamino group equatorial is favored in all considered solvents.     

Twisting of glycosidic bonds by hydrolases

Patterns of scissile bond twisting have been found in crystal structures of glycoside hydrolases (GHs) that are complexed with substrates and inhibitors. To estimate the increased potential energy in the substrates that results from this twisting, we have plotted torsion angles for the scissile bonds on hybrid Quantum Mechanics::Molecular Mechanics energy surfaces. Eight such maps were constructed, including one for α-maltose and three for different forms of methyl α-acarviosinide to provide energies for twisting of α-(1,4) glycosidic bonds. Maps were also made for β-thiocellobiose and for three β-cellobiose conformers having different glycon ring shapes to model distortions of β-(1,4) glycosidic bonds. Different GH families twist scissile glycosidic bonds differently, increasing their potential energies from 0.5 to 9.5 kcal/mol. In general, the direction of twisting of the glycosidic bond away from the conformation of lowest intramolecular energy correlates with the position (syn or anti) of the proton donor with respect to the glycon’s ring oxygen atom. This correlation suggests that glycosidic bond distortion is important for the optimal orientation of one of the glycosidic oxygen lone pairs toward the enzyme’s proton donor.     

Preparation of 6-aminohexyl d-aldopyranosides

6-Aminohexyl glycosides covalently linked to solid matrices are effective reagents for the isolation of proteins that bind to carbohydrates [Schnaar and Lee, Biochemistry, 14 (1975) 1535–1541], and for the study of interactions between intact cells and immobilized carbohydrates [Weigel et al., J. Biol. Chem., 253 (1978) 330–333]. The preparation of the 6-aminohexyl glycosides of the following D-pyranoses is now described: β-glucose, β-galactose, 2-acetamido-2-deoxy-β-glucose, α-mannose, β-maltose, β-melibiose, β-lactose, and β-cellobiose. These glycosides were prepared by glycosylation of 6-(trifluoroacetamido)hexanol with the appropriate acetylated glycosyl halide in 1:1 (v/v) benzene-nitromethane, with mercuric cyanide as the catalyst. Deacylation of the glycosides was achieved in two steps: use of sodium methoxide for O-deacetylation, and of an anion-exchange resin for N-de(trifluoroacetyl)ation.     

Attribution des signaux de résonance magnétique nucléaire-13c de disaccharides peracétylés dans la série du D-glucose

Selective, double irradiation allows the assignment of most ¹³C-n.m.r. signals in a series of per-O-acetyl disaccharides composed of two D-glucose residues linked α-(1→3), β-(1→3), α-(1→4), β-(1→4), α-(1→6), β-(1→6), and α,α-(1→1). The main influences that affect the chemical shifts are discussed and the spectra of β-cellobiose octaacetate and β-maltose octaacetate are compared to those of cellulose and amylose triacetate, respectively, to show the possibilities and limitations of a disaccharide model for the interpretation of the ¹³C-spectrum of a polymer.     

Enantiomer-Selective Photo-Induced Reaction of Protonated Tryptophan with Disaccharides in the Gas Phase

In order to investigate chemical evolution in interstellar molecular clouds, enantiomer-selective photo-induced chemical reactions between an amino acid and disaccharides in the gas phase were examined using a tandem mass spectrometer containing an electrospray ionization source and a cold ion trap. Ultraviolet photodissociation mass spectra of cold gas-phase noncovalent complexes of protonated tryptophan (Trp) enantiomers with disaccharides consisting of two d-glucose units, such as d-maltose or d-cellobiose, were obtained by photoexcitation of the indole ring of Trp. NH₂CHCOOH loss via cleavage of the C_α–C_β bond in Trp induced by hydrogen atom transfer from the NH₃ ⁺ group of a protonated Trp was observed in a noncovalent heterochiral H⁺(l-Trp)(d-maltose) complex. In contrast, a photo-induced chemical reaction forming the product ion with m/z 282 occurs in homochiral H⁺(d-Trp)(d-maltose). For d-cellobiose, both NH₂CHCOOH elimination and the m/z 282 product ion were observed, and no enantiomer-selective phenomena occurred. The m/z 282 product ion indicates that the photo-induced C-glycosylation, which links d-glucose residues to the indole moiety of Trp via a C–C bond, can occur in cold gas-phase noncovalent complexes, and its enantiomer-selectivity depends on the structure of the disaccharide.     

Proton magnetic resonance spectra of methyl β-d-glucopyranoside tetranitrate and β-cellobiose octanitrate

The ¹H-n.m.r. spectra of methyl β-d-glucopyranoside tetranitrate and β-cellobiose octanitrate have been obtained with a 220-MHz spectrometer operated in the Fourier-transform mode. Interpretation of the spectra from first-order analysis is presented. The chemical shifts and coupling constants of all protons in these two molecules have been calculated with the LAOCN 3 computer program. The simulated spectra obtained with the KOMBIP program are given.     

Peptides and Peptoids - A Systematic Structure Comparison

A systematic analysis of the conformational space of the basic structure unit of peptoids in comparison to the corresponding peptide unit was performed based on ab initio MO theory and complemented by molecular mechanics (MM) and molecular dynamics (MD) calculations both in the gas phase and in aqueous solution.The calculations show three minimum conformations denoted as C_7ß, a_D and a that do not correspond to conformers on the gas phase peptide potential energy hypersurface. The influence of aqueous solvation was estimated by means of continuum models. The MD simulations indicate the a_D form as the preferred conformation in solution both in cis and trans peptide bond orientations.     

Individual scale factor approach for the vibrational circular dichroism similarity-guided spectral and conformational analysis of perezone and dihydroperezone

Evaluation of DFT calculated vibrational parameters for the IR and VCD spectra similarity of perezone ( 1 ) and dihydroperezone ( 2 ) was undertaken. Conformational sets were obtained using different search engines, and the parameters needed for spectra prediction were obtained using several combinations of commonly employed functionals and basis sets, and then weighted spectra were generated and compared with observed traces to provide infrared similarity (S_IR) and enantiomeric similarity index (ESI) values. These values evidenced a poor performance of the evaluated levels of theory that were overcome when using the individual scaling factors approach, providing 16% to 139% increases of the ESI values. The best performing level of theory was the B3LYP/DGDZVP2 with ESI values of 0.722 and 0.792 for 1 and 2 . Moreover, a correlation analysis showed that the irregular DFT performance arises from rotational strength deviations, which suggests to discard conformational abundance accuracy as the main source of differences. Furthermore, a similarity guided conformational analysis showed that conformations with high ESI values prefer particular orientations of the C C bonds directly attached to the stereogenic carbon atom, with more distant dihedral angles having less influence. Additionally, folded and extended conformers appear to be equally capable to yield high individual ESI values, although abundances of folded conformers just account for 16% of the total population. Nevertheless, abundance optimization showed that a high ESI similarity value of 0.834, is possible when the population of these conformers is increased to 26%, suggesting that a larger abundance of these conformers might be present in solution.     

The conformational properties of dehydrobutyrine and dehydrovaline: theoretical and solid‐state conformational studies

Dehydrobutyrine is the most naturally occurring dehydroamino acid. It is also the simplest dehydroamino acid having the geometrical isomers E/Z. To investigate its conformational properties, a theoretical analysis was performed on N‐acetyl‐α,β‐dehydrobutyrine N′‐methylamides, Ac‐(E)‐ΔAbu‐NHMe and Ac‐(Z)‐ΔAbu‐NHMe, as well as the dehydrovaline derivative Ac‐ΔVal‐NHMe. The ?, ψ potential energy surfaces and the localised conformers were calculated at the B3LYP/6‐311 + + G(d,p) level of theory both in vacuo and with inclusion of the solvent (chloroform, water) effect (SCRF method). The X‐ray crystal structures of Ac‐(Z)‐ΔAbu‐NHMe and Ac‐ΔVal‐NHMe were determined at 85 and 100 K, respectively. The solid‐state conformational preferences for the studied residues have been analysed and compared with the other related structures. Despite the limitations imposed by the C^α = C^β double bond on the topography of the side chains, the main chains of the studied dehydroamino acids are more flexible than in standard alanine. The studied dehydroamino acids differ in their conformational preferences, which depend on the polarity of the environment. This might be a reason why the nature quite precisely differentiates between ΔVal and each of the ΔAbu isomers, and why, particularly so with the latter, they are used as a conformational tool to influence the biological action of usually small, cyclic dehydropeptides. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.     

Fermentation of C14-Labeled Cellobiose by Cellulomonas fimi

Crude cell-free extracts from Cellulomonas fimi contain cellobiose phosphorylase which cleaves cellobiose into glucose and glucose-1-phosphate in the presence of inorganic phosphate. With the aid of this enzyme, two samples of C¹⁴-cellobiose labeled in reducing or non-reducing glucosyl moiety were prepared from uniformly labeled C¹⁴-glucose or C¹⁴-glucose-1-phosphate as substrate, respectively. The labeled preparations have been shown to be radiochemically pure. Analyses of the anaerobic fermentation products from C¹⁴-cellobiose by resting cell suspensions showed that both glucose moieties were fermented almost equivalently. However, relatively small differences in specific activities of the products revealed that significantly larger amounts of formic acid and smaller amounts of acetic acid were produced from the reducing glucose moiety than from the other half of the molecule. Succinic and lactic acids appeared to be produced almost equally from both moieties.     

Linear oligopeptides: c.d. and n.m.r. study of Dnp-pNA derivatives of Aib-containing tetrapeptides in a β-bend conformation

A circular dichroism investigation of two β-bend forming, Aib-containing tetrapeptides, with the -Aib-l-Ala- and -l-Ala-Aib- central sequences, occurring in peptaibol antibiotics, blocked at the N-terminal end with the 2,4-dinitrophenyl group and at the C-terminal end with the p-nitroanilino group, is described. A comparison is made with a tetrapeptide containing the -l-Ala-l-Ala- central sequence, also observed in peptaibol antibiotics. The amount of β-bend conformers, determined from the intensities of the exciton couplets arising from the intramolecular interaction of the p-nitroanilino chromophores, has been assessed as a function of the hydrogen-bonding properties of the solvent. The conformational analysis in dimethylsulphoxide has been extended to ¹H nuclear magnetic resonance. Some information on the type of β-bend formed has additionally been obtained. The preparation and characterization of the three chromophoric tetrapeptides, along with some analogues and synthetic precursors, are also reported.     

Structure and Dynamics of Elastin Building Blocks. Boc-LG-OEt,Boc-VG-OEt,Boc-VGG-OH

Abstract

Short di- and tripeptides such as Boc-LG-OEt, Boc-VG-OEt and Boc-VGG-OH, corresponding to abundant repetitive sequences in elastin, have been extensively studied both in solid state, by X-ray diffraction, and in solution by circular dicroism and nuclear magnetic resonance. Furthermore, theoretical procedures such as simulated annealing and molecular dynamics were also performed on these peptides.

In general, the results indicate that no one single structure (be folded or extended) could be representative for these sequences in the protein, but rather that a multiplicity of interconverting conformers, ranging from folded to extended structures, should be considered. In any case, these structures, e.g. β-turns, polyglycine II and β-conformations, are those previously suggested to participate to conformational equilibria of elastin.     

The effect of adjacent charges on the kinetics of rotation of the peptide bond

The kinetics of rotation of the peptide (amide) bond in dimethylacetamide, glycine dimethylamide, N-acetylsarcosine, and glycylsarcosine have been studied in basic, neutral, and acidic aqueous solutions by proton magnetic resonance spectroscopy. The data indicate that the presence of nearby negative or positive charges do not greatly perturb the energetics of conformational equilibration about the amide carbon-nitrogen bond. In N-acetylsarcosine and glycylsarcosine two distinguishabe conformers are present; their relative abundance is essentially 50%/50% except at low pH. It is suggested that intramolecular hydrogen bonding is responsible for deviations from this population ratio. The activation enthalpies (ΔH?) for rotation appear to be linearly related to the corresponding activation entropies (ΔS?) leading to an isokinetic temperature of about 400°K.