Molecular dynamics simulation of oligosaccharides containing N-acetyl neuraminic acid

αD -N-acetyl neuraminic acid (Neu5Ac, sialic acid) is a commonly occurring carbohydrate residue in various cell surface glycolipids and glycoproteins. This residue is linked terminally or internally to Gal residues via an α(2 → 3) or α(2 → 6) linkage. In the cell surface receptor, sialyl-Lewis^X, a terminal α(2 → 3) linkage is present. Previous studies from our laboratory have shown that in solution Lewis^X adopts a relatively rigid structure. In order to model the Neu5Ac residue, vacuum molecular dynamics of this monosaccharide were compared with simulations that explicitly include solvent water. The dynamical average of the monosaccharide conformation obtained from the two simulations was similar. Vacuum calculations for the disaccharide Neu5Ac α(2 → 3) Gal β-O-methyl show that a number of low energy minima are accessible to this disaccharide. Molecular dynamics simulations starting from the low energy minima show conformational transitions with a time scale of 10–50 ps among several of the minima while large barriers between other minima prevent transitions on the time scale studied. Simulations of this disaccharide in the presence of solvent show fewer conformational transitions, illustrating a dampening effect of the solvent that has been observed in some other studies. Our results are most consistent with an equilibrium among multiple conformations for the Neu5Ac α(2 → 3) Gal β linkage. © 1994 John Wiley & Sons, Inc.     

Circular dichroism study of polyriboxanthylic acid.

We report in the present paper the circular dichroism spectra of poly(X) at different pH and temperature values. The spectra are characteristic of three stable forms of poly(x) in the pH range of protonation of xanthosine. An electrostatic barrier is proposed to account for the hysteresis and metastability observed in a certain pH range. Some results on oligo(X) at basic pH are also presented. Poly(X) at basic pH is investigated also by hydrodynamic techniques.     

Circular dichroism of the nucleic acid monomers.

Circular dichroism spectra of the nucleic acid monomers have been measured in aqueous solution and extended into the vacuum ultraviolet region to about 166 nm. Measurements were made on ribo and deoxyribo derivatives of adenine, guanine, hypoxanthine, cytosine, thymine, and uracil derivatives both with and without the 5′-phosphate (with the exception of ribosyl thymine 5′-phosphate). Absorption spectra of the deoxyribonucleotides measured to about 175 nm are also presented. The results demonstrate that both the circular dichroism and absorption spectra observed below 200 nm are no more complicated than the spectra normally recorded above 200 nm. In most cases, the circular dichroism spectra of the various derivatives of a given base are similar, indicating that the conformations are similar. On the other hand, the differences among the circular dichroism spectra of the various derivatives of a given base are sufficient to identify a particular derivative. The average circular dichroism for the deoxyribonucleotides is compared with the circular dichroism of native E. coli DNA. The comparison reveals that the circular dichroism of DNA below 200 nm is due principally to the interaction between the bases rather than the intrinsic circular dichroism of the monomers. The monomer transitions are discussed in relationship to the absorption and circular dichroism spectra presented.     

Circular dichroism of adenine and thymine containing synthetic polynucleotides

Circular dichroism (CD) spectra of poly(dA), poly(dT), poly(dA)·poly(dT), and poly[d(A-T)]·poly[d(T-A)] have been measured as a function of temperature. From these data difference spectra have been calculated by subtracting the spectrum measured at low temperature from the spectra measured at higher temperatures. The CD difference spectra obtained upon melting of the two double-stranded polymers are very similar. From a comparison of these difference spectra with calculated ones it is shown that optical transitions near 272 nm (on A) and 288 nm (most probably on T) are present. The premelting changes of the CD spectrum of poly[d(A-t)]·poly[d(T-A)] are due to a change in conformation in which the secondary structure goes from a C- to B-type spectrum by increasing the A-type nature of the polymer. Such a change is not observed for poly(dA)·poly(dT). Instead, a transition between two different B-type geometries occurs.     

Circular dichroism studies on flavoproteins containing covalently bound coenzymes

Absorption and circular dichroism spectra of cholesterol oxidase from Schizophyllum commune and choline oxidase from Alcaligenes sp. were measured and compared. The prosthetic group of cholesterol oxidase is 8 alpha-[N(1)-histidyl]-FAD (1, 2), while that of choline oxidase is 8 alpha-[N(3)-histidyl]-FAD (3). In the CD spectra of the two enzymes in either the oxidized or reduced state, the corresponding bands in the visible region are of approximately the same intensity and shape but of opposite sign. A notable feature in the CD spectra of the two enzymes after light irradiation is the appearance of a CD band in the longer wavelength region (550-650 nm) and the opposite signs of the CD band in this region in the two enzymes. The similarity of the shape and intensity of the CD spectra of the two enzymes suggests that the environments surrounding the flavin moieties are very similar, and the sign reversal of the CD bands suggests that the mutual orientations between the transition moment of flavin and that of its environment differ in the two enzymes.     

Circular dichroism calculations for polyinosinic acid in proposed multi-stranded geometries.

Circular dichroism spectra have been calculated for multi-stranded polyinosinic acid using three different right-handed structures proposed from X-ray diffraction studies. Agreement between calculated spectra and spectra measured at high salt concentration is best for a four strand structure in which the bases are tilted with respect to the helix axis, as proposed by Arnott et al. (1974). For structures in which the bases are perpendicular to the helix axis, the characteristic negative circular dichoroism of polyinosinic acid at long wavelength no longer appears in the calculated spectra. It is clear that a negative circular dichroism at long wavelength does not indicate a left-handed polynucleotide helix.     

Circular dichroism of some mononucleosides.

The circular dichroism (CD) and absorption spectra of uridine, thymidine, purine ribonucleoside, and the four adenine derivatives 2′-deoxyadenosine, adenosine, adenosine-3′,5′-cyclic phosphate, and arabinosyl adenine were measured in water at pH 7 and pH 2. The absorption and CD spectra of the pyrimidines were simultaneously fitted to four Gaussian bands, and the dipole and rotational strengths of the electronic transitions determined. Adenine-derivative CD spectra were determined by computer averaging six runs. The spectra showed CD bands at 268, 226, 209, and 195 nm. The band at 226 nm probably is an n–π* transition; the band at 209 nm cannot be detected without a computer. The CD and absorption spectra of purine ribonucleoside indicate three transitions in the 230–310-nm region.     

Circular dichroism of soybean leghemoglobin.

Circular dichroic (CD) spectra of soybean leghemoglobin, and some of its liganded derivatives were measured over the wavelength range of 650 to 200 nm. The heme-related circular dichroic bands in the visible, Soret and ultraviolet wavelength regions exhibit Cotton effects characteristic of each of the compounds examined. The positions of the dichroic bands vary with ligand substitutions and the oxidation state of the iron. All leghemoglobin derivatives, except the apoprotein, exhibit negative circular dichroic bands in the region of Soret absorption. In this region the optical activity of compounds with high-spin moments is greater than that of compounds with low or intermediate spin moments. The ellipticity of the heme band at about 260 nm is also altered by ligand binding and spin state. The dichroic spectra in the far-ultraviolet region indicated a high extent of alpha-helical structure (about 70%) in the native leghemoglobin and its liganded derivatives. The helicality of the apoprotein seems to diminish suggesting a decrease caused by the removal of the heme.     

Circular dichroism studies of ampullosporin-A analogues.

Ampullosporin A (AmpA), a 15mer peptalbol containing seven Aib residues is able to induce pigmentation on Phoma destructiva and hypothermia in mice, as well as to exhibit a neuroleptic effect. A circular dichroism study of ampullosporin A and its analogues was carried out in organic solvents with different polarities and detergent micelles to determine the relationship between their conformational flexibility and biological activities. The analogues were obtained by modifying the N- and C-termini of ampullosporin A. Furthermore, Gln and Leu were systematically substituted by Ala and Aib residues were replaced by Ala and/or Ac6c. To estimate the helicity of the analogues, the CD spectrum of AmpA recorded in acetonitrile was correlated to its crystal structure. All analogues displayed similar CD curve shapes in organic solvents with the ratio between two negative band intensities R = [theta]n-pi*/[theta]pi-pi* < 1. In acetonitrile, most of the analogues adopted a 70%-85% helical structure, which was higher than the average of 40%-60% obtained in TFE. In detergent micelles, the analogues were distinguishable by their CD profiles. For most of the biologically active analogues, the CD spectra in detergent micelles were characterized by a R ratio > 1 and increased helicity compared with those recorded in TFE, suggesting that the interaction of the peptides with the membrane and peptide association was necessary for their hypothermic effect.