Quantum chemical studies on the conformational structure of bacterial peptidoglycan. II. PCILO calculations on the mono-saccharides

Conformational energy calculations were performed on mono-saccharides of the glycan moiety of bacterial peptidoglycan using PCILO semiempirical quantum chemical method to re-examine the preferred conformations of these molecules so far reported in the empirical studies. The PCILO dihedral angles for some side groups are different from those found in MNDO studies. However, in almost every case the PCILO and empirical calculations suggest the same orientations for the different side groups. Moreover, the strengths of the hydrogen bonds between several groups found in the PCILO calculations are more than those of the empirical and MNDO results.     

Quantum chemical studies on the conformational structure of bacterial peptidoglycan. I. MNDO calculations on the glycan moiety

Semi-empirical quantum chemical calculations at MNDO level of approximations have been carried out on the monosaccharide and disaccharide moiety of bacterial peptidoglycan to determine the energetically favoured conformation of their side groups and the relative orientations of sugar rings. The results have been compared with those obtained from empirical energy calculations. The MNDO results have also been discussed with available experimental data and suggest that a chitin-like structure is not favoured for the glycan moiety of peptidoglycan.     

Quantum chemical studies on the conformational structure of nucleic acids. IV. Calculation of backbone structure by CNDO method

Quantum chemical calculations using the CNDO/2 method, have been carried out to determine the energetically favoured ranges of the torsional angles (φ′, ω′, ω, φ, ψ) which fix the conformational structure of nucleic acid backbone. The two dimensional isoenergy maps have been constructed in the (ω′, ω) and (φ, ψ) hyperspaces. The variation of total energy with respect to φ′ has also been studied. The results show that the non-bonding interactions play a major role in the conformational stability of nucleic acids and polynucleotides. The theoretical predictions show good correspondence with the experimental data (X-ray and ¹³C NMR) as well as the other reported theoretical calculations (EHT, PCILO and classical potential functions). The most favoured structure has the conformational angles close to 240, 290, 290, 180 and 60° and these values lead to a helical structure with a pitch of 34 Å and about ten nucleotide units per turn of the helix. The proposed models of Watson &; Crick, DNA-B and DNA-C lie in high energy regions.     

CNDO calculations on the conformational structure of acetylcholine

Molecular orbital theory in the CNDO framework has been used to calculate the torsional angles which lead to minimum energy conformations in acetylcholine. The calculated angles agree well with the experimental observations on acetylcholine and its derivatives. The results have been compared with the earlier predictions based on extended Hückel theory and van der Waal pairwise interactions.     

Quantum chemical studies of protein structure

Quantum chemical methods now permit the prediction of many spectroscopic observables in proteins and related model systems, in addition to electrostatic properties, which are found to be in excellent accord with those determined from experiment. I discuss the developments over the past decade in these areas, including predictions of nuclear magnetic resonance chemical shifts, chemical shielding tensors, scalar couplings and hyperfine (contact) shifts, the isomer shifts and quadrupole splittings in M?ssbauer spectroscopy, molecular energies and conformations, as well as a range of electrostatic properties, such as charge densities, the curvatures, Laplacians and Hessians of the charge density, electrostatic potentials, electric field gradients and electrostatic field effects. The availability of structure/spectroscopic correlations from quantum chemistry provides a basis for using numerous spectroscopic observables in determining aspects of protein structure, in determining electrostatic properties which are not readily accessible from experiment, as well as giving additional confidence in the use of these techniques to investigate questions about chemical bonding and chemical reactions.     

CNDO/2 quantum-mechanical calculations of the conformational flexibility of the diketopiperazine skeleton

Eight conformers typical of diketopiperazine (DKP) ring folding were chosen for analysis. Conformational energy calculations were carried out using the semiempirical quantummechanical CNDO/2 method. The results obtained confirm considerable flexibility of the DKP skeleton. As the degree of folding increases, twisted boat conformations with the nonplanar peptide bonds tend to be more stable, while more rigid regular boat conformations with planar peptide bonds appear to be less stable than a flat one. The CNDO/2 method was found to be reliable enough for conformational studies of cyclic peptide skeletons with cis-peptide bonds.     

Synthesis and conformational analysis of the repeating units of bacterial spore peptidoglycan

Deprotection of the fully blocked disacharide allyl O-(2-amino-4,6-O-benzylidene-3-O-[(R)-1-carboxyethyl]-2-deoxy-beta-D-glucopyranosyl-1',2-lactam)-(1-->4)-2-acetamido-3,6-di-O-benzyl-2-deoxy-beta-D-glucopyranoside by selective de-O-allylation and parallel removal of the benzylidene and O-benzyl groups is described. The resulting beta-muramyl lactam-(1-->4)-GlcNAc disaccharide is characterised as the per-O-acetylated derivative by 1H and 13C NMR spectroscopy and X-ray structure analysis. Conformational analysis about glycosidic bond of repeating units of bacterial spore cortex is based on experimental data and molecular modelling.     

Quantum chemical studies on the aminopolynitropyrazoles

We have explored the geometric and electronic structures, band gap, thermodynamic properties, density, detonation velocity and detonation pressure of aminopolynitropyrazoles using the density functional theory (DFT) at the B3LYP/aug-cc-pVDZ level. The calculated detonation velocity and detonation pressure, stability and sensitivity of model compounds appear to be promising compared to the known explosives 3,4-dinitro-1 H-pyrazole (3,4-DNP), 3,5-dinitro-1 H-pyrazole (3,5-DNP), hexahydro-1,3,5-trinitro-1,3,5-triazinane (RDX) and octahydro-1,3,5,7-tetranitro-l,3,5,7-tetraazocane (HMX). The position of NH₂ group in the polynitropyrazoles presumably determines the structure, stability, sensitivity, density, detonation velocity and detonation pressure.     

Molecular modelling of the three-dimensional structure and conformational flexibility of bacterial lipopolysaccharide.

Molecular modelling techniques have been applied to calculate the three-dimensional architecture and the conformational flexibility of a complete bacterial S-form lipopolysaccharide (LPS) consisting of a hexaacyl lipid A identical to Escherichia coli lipid A, a complete Salmonella typhimurium core oligosaccharide portion, and four repeating units of the Salmonella serogroup B O-specific chain. X-ray powder diffraction experiments on dried samples of LPS were carried out to obtain information on the dimensions of the various LPS partial structures. Up to the Ra-LPS structure, the calculated model dimensions were in good agreement with experimental data and were 2.4 nm for lipid A, 2.8 nm for Re-LPS, 3.5 nm for Rd-LPS, and 4.4 nm for Ra-LPS. The maximum length of a stretched S-form LPS model bearing four repeating units was evaluated to be 9.6 nm; however, energetically favored LPS conformations showed the O-specific chain bent with respect to the Ra-LPS portion and significantly smaller dimensions (about 5.0 to 5.5 nm). According to the calculations, the Ra-LPS moiety has an approximately cylindrical shape and is conformationally well defined, in contrast to the O-specific chain, which was found to be the most flexible portion within the molecule.     

Enantioselective autocatalysis. III. Configurational and conformational studies on a 1,4-benzodiazepinooxazole derivative

We report here on configurational and conformational studies undertaken on the bromofluoro-1,4-benzodiazepinooxazole derivative I, which has previously been found capable of undergoing total spontaneous resolution under racemizing conditions. Due to its bridgehead N-atom I may exist in any of four diastereomeric forms,C _r N _r (orC _s N _s ) andC _r N _s (orC _s N _r ). Molecular mechanics calculations revealed that in their lowest energy conformations theC _r N _r (orC _s N _s ) diastereomers were favored over theC _r N _s (orC _s N _r ) diastereomers by some 3.42 kcal/mol, while semi-empirical quantum mechanical calculations indicated heats of formation also favoring theC _r N (orC _s N _s ) diastereomers by 3.83 kcal/mol. The¹H NMR spectra of the three crystalline modifications (, and) of I were examined in acetone, and found to be identical. These data, combined with the results of the above calculations, suggest that I exists in methanol or methanol-acetone solutions as theC _r N (orC _s N _s ) enantiomer prior to its racemization.     

Lipid intermediates in the biosynthesis of bacterial peptidoglycan.

This review is an attempt to bring together and critically evaluate the now-abundant but dispersed data concerning the lipid intermediates of the biosynthesis of bacterial peptidoglycan. Lipid I, lipid II, and their modified forms play a key role not only as the specific link between the intracellular synthesis of the peptidoglycan monomer unit and the extracytoplasmic polymerization reactions but also in the attachment of proteins to the bacterial cell wall and in the mechanisms of action of antibiotics with which they form specific complexes. The survey deals first with their detection, purification, structure, and preparation by chemical and enzymatic methods. The recent important advances in the study of transferases MraY and MurG, responsible for the formation of lipids I and II, are reported. Various modifications undergone by lipids I and II are described, especially those occurring in gram-positive organisms. The following section concerns the cellular location of the lipid intermediates and the translocation of lipid II across the cytoplasmic membrane. The great efforts made since 2000 in the study of the glycosyltransferases catalyzing the glycan chain formation with lipid II or analogues are analyzed in detail. Finally, examples of antibiotics forming complexes with the lipid intermediates are presented.     

Immunoelectron microscopic studies on the localization of peptidoglycan peptide subunit pentapeptides in bacterial cell walls

The peptide subunit pentapeptide H-L-Ala-D-Glu(L-Lys-D-Ala-D-Ala-OH)-NH₂ of peptidoglycan was localized in the cell walls of several Gram-positive bacteria employing the indirect immunoferritin technique. Specific antibodies to the D-alanyl-D-alanine moiety of non-crosslinked peptide subunit pentapeptide were raised in rabbits by immunization with synthetic immunogen albumin-(CH₂CO-Gly-L-Ala-L-Ala-D-Ala-D-Ala-OH)₃₉. Specificity of these antibodies for the peptide subunit pentapeptide and not for the peptide subunit tetrapeptide was corroborated in a Farr-type radio-active hapten binding assay. Specificity of labelling with ferritin was established by immunoelectron microscopic controls, and by the excellent correlation between specific labelling of cells with ferritin and the particular peptidoglycan primary structure of bacterial strains investigated. Cells of Lactobacillus gasseri, Streptococcus pyogenes and Staphylococcus aureus revealing non-crosslinked peptide subunit pentapeptides in their peptidoglycans could specifically be labelled. Lactobacillus acidophilus and Bacillus subtilis, on the contrary, missing such pentapeptides, failed in labelling.The implication of this method to possibly localize the points of attack of penicillin or cycloserine is discussed.Abbreviations used meso-A₂pm meso-diaminopimelic acid - DSM Deutsche Sammlung für Mikroorganismen, Göttingen, FRG This paper is dedicated to Professor Gerhart Drews on the occasion of his 60th birthday     

DFT-GIAO study of aryltetralin lignan lactones: conformational analyses and chemical shifts calculations

The conformational properties of polygamain and morelensin, two aryltetralin lignan lactones, have been investigated in both the gas-phase and chloroform solution using DFT calculations at the B3LYP/6-311G(d,p) level. Results indicate that the conformation of polygamain is very rigid. Thus, the conformational flexibility of its five-membered rings is considerably restricted as reflects the pseudorotational parameters of the corresponding envelope conformations. On the other hand, morelensin shows a notable conformational flexibility, which is mainly due to its two methoxy groups. Accordingly, 16 minimum energy conformations with relative energies smaller than 2.4 kcal/mol were detected. Furthermore, chemical shifts for 13C nuclei have been calculated using the GIAO method, results being compared with experimental data. A good agreement was found for both polygamain and morelensin.     

Structure of poly 8-bromoadenylic acid; conformational studies by CPF energy calculations.

Poly 8-bromoadenylic acid [poly(BBrA)] is the only known all-syn polynucleotide. It shows a helix-coil transition with a melting curve centred around 55 degrees C. Energy calculations based on classical potential functions have been used to explore the three-dimensional structure of this polymer in helix and random coil. It is concluded that the ordered state is a helix of two parallel strands with a two-fold rotation axis, and the duplex is stabilised by hydrogen bonds involving N1 and H6. Each strand has a conformation with C3' endo geometry, phi' = 216 degrees, omega' = 280 degrees, omega = 294 degrees, phi = 179 degrees, chi = 243 degrees and psi = 57 degrees. Such a conformation leads to approximately 8 nucleotide units per turn of the helix and an axial rise of 3.9A degrees. The structure of poly(8BrA) has been compared with that of the related polymer poly(A) which forms a double helical structure in acidic conditions with bases in the anti conformation and with interstrand hydrogen-bonds between N7 and H6. This is the first time that a specific geometrical model of a novel polynucleotide structure has been produced initially by potential energy calculations, though such calculations on a number of known structures have been reported previously.