Adenine Nucleosides in Solution: Circular Dichroism Studies and Base Conformation

Abstract

Adenosine, AMP, S-adenosylhomocysteine, S-adenosylmethionine, aristeromycin and 25 other synthetic adenosine analogs modified in the 4' or 5' positions show certain groups of different circular dichroism (CD) spectra. Both positive and negative Cotton effects can occur in the long-wavelength part (250-270 nm) of the spectra. Molar ellipticities [O] range from -6000 (in adenosine 5'-carboxylate) to + 4000 deg. cm2 dmol-l (in 5'-deoxy-5'iodoadenosine), including some compounds with small, polar 5'-substituents in which low-intensity bands are found in signed pairs. Most of these adenosine derivatives that have the same adenine chromophore and a ribofuranose moiety unsubstituted in the 2' and 3' positions prefer an anti-conformation of the adenine base, as evidenced by proton magnetic resonance spectroscopy. In the majority of cases, electronic perturbations of the chromophore or major alterations of the assymmetric sugar residue can be excluded as sources of the C D variations. Therefore a correlation of the long-wavelength C D bands with the glycosyl torsion angle bCN is suggested, where the gauche, gauchelanti combination which is typical of AMP in the crystal and in solution (&.N zz -40 ', [el negative) is one reference point and a region for &N = 0 'is assigned to compounds with space-filling substituents such as S-adenosylmethionine. Both negative and positive Cotton effects can be associated with the anti conformation range. Within this series, the base conformation of novel nucleoside structures could be predicted from CD measurements. The C D spectrum gives no indication, however, of whether a certain torsion angle is the result of a rigid structure (as in AMP) or the average value of a molecule with high rotational freedom (as in 5'-deoxyadenosine). The conformations of aristeromycin and 4'-thioadenosine are discussed in relation to adenosine, and a structure-determining effect of the 4' bridge atom is noted. Circular dichroism (CD) and, in earlier years, optical rotatory dispersion (ORD) spectroscopy have become useful tools for the study of conformation changes in nucleic acids, pol ynucleotides, and nucleosides or mononucleotides [l]. Like nuclear magnetic resonance, these techniques are valuable because they provide information about the state of the molecules in dilute solutions resembling physiological conditions of pH, ionic strength, and concentration. Several authors have described correlations of the sign of Cotton effects in pyrimidine and purine nucleosides with the sugar-base torsion angle &N [2] about the glycosidic bond, based upon empirical assignments important result of these studies is the reversion of long-wavelength Cotton effects found in compounds in which the base is forced out of its regular anticonformation by bulky substituents at the 6 or 8 position of a pyrimidine or purine ring, respectively [9]. The ORD and C D spectra of anomeric pentofuranosides have also been well documented [lo, 111. Studies of magnetic circular dichroism (the Faraday effect) have provided precise resolu...

The Binding of fd Gene 5 Protein to Polydeoxynucleotides: Evidence from CD Measurements for Two Binding Modes

“…We did not find any increase in the , and single-stranded DNA were much like those induced by the binding of T4 gene 32 protein (39)(40)(41)(42), in that the CD above 250 nm became less positive or even negative, although the spectra of the polymers bound by the two proteins differed in shape. Although it is not known what does cause such changes in the CD spectra of DNAs, they can probably be accounted for by small changes in secondary conformation combined with changes in the environment or glycosyl torsion angles of individual nucleotide residues (43)(44)(45)(46)(47)(48). It seems unlikely to us that such CD changes arose from gene 5 protein chromophores that were specifically altered to become optically active when A or T nucleotides were bound, but not when I or C nucleotides were bound.…”

A consistent S-Adenosylmethionine force field improved by dynamic Hirshfeld-I atomic charges for biomolecular simulation

“…The D-HI charges with the optimized parameters for the CT-CT-S-CT dihedral angle constitutes a set of parameters which reproduces the experimental NOE distances and experimentally observed conformations in aqueous solution obtained by other spectroscopy techniques as UV, IR and Circular Dichronism [11][12][13]. These charges will reflect the average molecular electrostatic potential (MEP) of the polarized molecule due to the presence of the solvent, since the Hirshfeld-I method has been shown to reproduce the molecular electrostatic potential in vacuum (see above) and the inclusion of the solvent as point charges in the molecular dynamics simulations should take into account the average polarization.…”

“…This confirms prior studies showing that the r 1=6 averaging of the NOE signal obtained experimentally is most sensitive to changes in the proton-proton distance distribution at short distances and not sensitive to capture notorious changes in the populations of more than one conformation when present [38][39][40]. Additional experimental observations based on IR and UV spectroscopy, Circular Dichronism and NMR spectroscopy conclude that the glycosidic bond might also adopt an anti conformation beside the syn conformation found in some protein crystals [11][12][13]. In terms of the experimental intramolecular NOE distances the distances H42-H44 and H42-H46 are most sensitive to changes in the glycosidic angle.…”

“…But it is inert at room temperature and low pH (3)(4)(5)(6)(7) for several hours [9,10]. Under these conditions spectroscopic ultraviolet and optical rotation data were interpreted with respect to a stable conformation with an anti configuration of the N29-C27 glycosidic bond [11][12][13] (see Fig. 1).…”

L‐Erythruronic Acid Derivatives as Building Blocks for Nucleoside Analogs. Synthesis of 4′‐C‐Aryl‐D‐ribonucleosides

“…Follmann has shown that a variety of CD. curves with both negative and positive Cotton effects in the long-and short-wavelength regions are observed for adenosine derivatives possessing a modified substituent at C (4') for which he assumed an anti-conformation [29] [30]. The difference of the CD.…”