Conformation Of Furanose Ring Research Articles

Synthesis of 4'-C-methylnucleosides.

Several 4'-C-methylnucleosides were prepared. 1H-NMR studies on these nucleotides showed that they have the 3'-exo furanose ring conformation different from the 3'-endo conformation of natural nucleosides.

Deoxygenated and alkylated furanoses: Thorpe—Ingold effects on tautomeric equilibria and rates of anomerization

2-Deoxy- d- glycero-tetrose, 3-deoxy- dl- glycero-tetrose, 3-deoxy-3,3-di- C-methyl- dl- glycero-tetrose, 3- C-methyl- dl-erythrose, 3- C-methyl- dl-threose, 2-deoxy-5- O-methyl- d- erythro-pentose and 3-deoxy-5- O-methyl- d- erythro-pentose have been prepared, in some cases with 13C-substitution at the anomeric carbon, and characterized by 1H- (300 and 620 MHz) and 13C-n.m.r. (75 MHz) spectroscopy. The proportions of cyclic (α and β furanoses) and acyclic (aldehyde and hydrate) forms were determined in aqueous ( 2H 2O) solution, and ring-opening ( k open) and ring-closing ( k close) rate constants were measured by 1H and 13C saturation-transfer n.m.r. spectroscopy at p 2H 5.0 (acetate buffer) and 60°. The degree of furanose ring substitution was found to significantly affect both the thermodynamics and kinetics of furanose anomerization. Increased substitution enhances the proportion of cyclic forms in solution by stimulating furanose k close. In contrast, furanose k open was less affected by the degree of substitution; however, kinetic studies of 2-deoxyfuranose anomerization implicate furanose ring conformation as a potential determinant of k open.

Visualisation of a 2′-5′ parallel stranded double helix at atomic resolution: crystal structure of cytidylyl-2′,5′-adenosine

X-ray crystallographic studies on 3'-5' oligomers have provided a great deal of information on the stereochemistry and conformational flexibility of nucleic acids and polynucleotides. In contrast, there is very little information available on 2'-5' polynucleotides. We have now obtained the crystal structure of Cytidylyl-2',5'-Adenosine (C2'p5'A) at atomic resolution to establish the conformational differences between these two classes of polymers. The dinucleoside phosphate crystallises in the monoclinic space group C2, with a = 33.912(4)A, b = 16.824(4)A, c = 12.898(2)A and beta = 112.35(1) with two molecules in the asymmetric unit. Spectacularly, the two independent C2'p5'A molecules in the asymmetric unit form right handed miniature parallel stranded double helices with their respective crystallographic two fold (b axis) symmetry mates. Remarkably, the two mini duplexes are almost indistinguishable. The cytosines and adenines form self-pairs with three and two hydrogen bonds respectively. The conformation of the C and A residues about the glycosyl bond is anti same as in the 3'-5' analog but contrasts the anti and syn geometry of C and A residues in A2'p5'C. The furanose ring conformation is C3' endo, C2' endo mixed puckering as in the C3'p5'A-proflavine complex. A comparison of the backbone torsion angles with other 2'-5' dinucleoside structures reveals that the major deviations occur in the torsion angles about the C3'-C2' and C4'-C3' bonds. A right-handed 2'-5' parallel stranded double helix having eight base pairs per turn and 45 degrees turn angle between them has been constructed using this dinucleoside phosphate as repeat unit. A discussion on 2'-5' parallel stranded double helix and its relevance to biological systems is presented.

Ab initio molecular orbital calculations on furanose sugars: a study with the 6–31G basis set

Ab initio molecular orbital calculations were performed on 2-deoxy-β- d- glycero-tetrofuranose ( 1) using the 6–31G * basis set to evaluate the effect of ring conformation on the molecular parameters (bond lengths, angles, and torsions). Geometric optimizations were conducted on the planar and ten envelope conformers of 1, and these data were compared to those obtained from previous calculations using the STO-3G and 3–21G basis sets. Conformational energy profiles derived from 3–21G and 6–31G * data were found to be qualitatively comparable. The effect of furanose ring conformation on key bond lengths ( e.g., CH, CO), bond angles ( e.g., COC), and bond torsions ( e.g., the exoanomeric C-1O-1 torsion) was examined, and a qualitative agreement was observed between the 3–21G and 6–31G * analyses. The results indicate that, for semi-quantitative ab initio studies of intact carbohydrates, the 3–21G basis set is sufficient, and that the STO-3G basis set should not be employed unless crude structural approximations are desired. The observed concerted behavior of CO bond lengths in the vicinity of the anomeric carbon of the aldofuranose ring has suggested a possible role of C-1O-1 bond orientation in affecting the mechanism of glycoside bond hydrolysis.

A Stereochemical Rationale for the Activity of Anti-HIV Nucleosides

Crystallographic studies have shown that, in the solid state, nucleosides active against the human immunodeficiency virus (HIV) generally exhibit moderate to extreme S-type furanose conformations (pseudorotational phase angle up to 215°). Following this lead, it is shown that using principles of conformational analysis, one can rationalize the activity or inactivity of other nucleoside analogues (including many not yet studied by X-ray methods) in terms of the effects of substituents on the furanose ring conformation. An analysis of the various 1,4 interactions of the O4′ lone pairs, O4′ itself, and the substituents on C2′ and C3′ shows that S-type conformations are stabilized (relative to N-type) in all the active ribose analogues, whereas this effect is absent in most inactive compounds. The gauche effect is a major determinant of activity, and the O4′ lone pairs, which have been neglected in many previous force field studies, may also be involved in stabilizing extreme S-type conformations. In such conformations (particularly for P > 180°) the + sc orientation of O5′ is destabilized, increasing access to the ap orientation, which may be more favourable for activity.

Conformation and Antiherpes Activity of 3′- and 5′-Azido and Amino Analogs of 5-Methoxymethyl-2′-Deoxyuridine

Abstract The molecular conformations of 3′- and 5′-azido and amino derivatives of 5-methoxymethyl-2′-deoxyuridine, 1, were investigated by nmr. The glycosidic conformation of 5-methoxymethyl-5′-amino-2′,5′-dideoxy-uridine, 5 had a considerable population of the syn form. The 5′-derivatives show a preference for the S conformation of the furanose ring as in 1. In contrast, the 3′-derivatives show preference for the N conformation. For 5-methoxymethyl-3′-amino-2′,3′-dideoxyuridine, 3, the shift towards the N state is pH dependent. The preferred conformation for the exocyclic (C4′,C5′) side chain is g+ for all compounds except 5 which has a strong preference for the t rotamer (79%). Compounds 1, 3 and 5 inhibited growth of HSV-1 by 50% at 2, 18 and 70 μg/ml respectively, whereas 2 and 4 were not active up to 256 μg/ml (highest concentration tested). The compounds were not cytotoxic up to 3,000 μM.

Furanose ring conformation: the application of ab initio molecular orbital calculations to the structure and dynamics of erythrofuranose and threofuranose rings

Ab initiao molecular orbital calculations have been conducted on four tetrofuranose anomers, ..cap alpha..- and ..beta..-D-erythrofuranose and ..cap alpha..- and ..beta..-D-threofuranose, to study the effect of ring conformation on molecular parameters (bond lengths, bond angles, bond torsions) and on total energies. Geometric optimizations of envelope and planar conformers were conducted using the STO-3G basis set; single-point calculations were also performed with the 3-21G basis set. Preferred solution conformations deduced from previous NMR studies are in good agreement with those predicted by calculation, indicating that the intrinsic structures of these furanoses dictate their preferred geometries, and that solvation by water (/sup 2/H/sub 2/O) does not appear to be a major conformational determinant. The ..beta..-D-erythro configuration, which is structurally related to the ..beta..-D-ribo configuration found in RNA, was found to have significantly different conformational behavior from the other three configurations.

A method for the determination of furanose ring coordinates in its pseudorotation circuit for different amplitudes of pucker.

Interconversion between energetically favored molecular conformations must proceed through less favored intermediate states. Thus, a knowledge of the nucleotide furanose ring conformations, other than the crystallographically well-determined ones, are of interest in investigating nucleotide conformational energies and dynamics. The sugar ring flexibility affects the conformation and dynamics of the monomer and determines the range of feasible nucleic acid secondary and tertiary structures. We have generated furanose geometries for varying amplitudes of pucker over its entire range of pseudorotation by making use of a ring closure procedure and the empirical dependence of endocyclic bond lengths and bond angles on sugar pucker. Atomic coordinates are tabulated here for the furanose ring at pseudorotation phase angle intervals of 9 degrees for the average amplitude (tau m) of pucker of 39 degrees as well as for decreased (20 degrees and 30 degrees) and increased (44 degrees) values of tau m. However, the coordinates for any values of P and tau m can be readily calculated.

Conformational Analysis of 6-Substituted Uridine Analogues: Crystal Structures of Uridine-6-Thiocarboxamide and 6-Cyanouridine

Abstract Crystal structure analyses of uridine-6-thiocarboxamide (I) and 6-cyanouridine (II) show that both structures adopt a syn conformation about the glycosyl bond. The conformation of I is similar to that of orotidine (III). The furanose ring conformation of I is C4′-exo, unusual for syn conformers, and is C3′-endo in II. These results have a bearing on the inhibition of orotidylate decarboxylase by the 5′-phosphate of I.

Vasoactivities of adenosine analogues in trout gill ( salmo gairdneri R.)

Various adenosine analogues phosphorylated or not, modified at the purine ring level or in the carbohydrate moiety, have been tested for their ability to induce a vasoconstriction in the arterio-arterial vascular bed of the trout gill. The structural integrity of the purine ring and the N-glycosidic bond are required for activity. The anti conformation of the molecule is preferable to the syn conformation. The basicity and/or the hydrogen bonding capabilities at the 6-position are important for the potency of the molecule. Substitutions which decrease the basicity of the 1-position decrease the activity and substitutions which reinforce the basicity (2-Cl adenosine) increase it. Alterations of the furanose ring conformation and the reduction of the hydrogen bonding capabilities of the 2′- and 3′-hydroxyls decrease the potency of the compound. Some substitutions in the 5′-position intensify the haemodynamic response. Thus, 5′-ethyl carboxamide adenosine is one order of magnitude more potent than adenosine. The addition of more than one phosphate in 5′-position (ADP, ATP) favours the effectiveness of the compound but a further elongation of the phosphate chain does not improve its potency. The α-β configuration of the phosphate chain is essential for the physiological effect. IMP, adenylosuccinate and all cyclic necleotides are devoid of haemodynamic activity. These results sustain the hypothesis of the presence of specific vascular purinergic receptors in the trout gill.

Structure of disodium guanosine 5'-phosphate heptahydrate

Na2[CgHllN2OgP].7H20, M r = 494.0,orthorhombic, C222~, a = 22.880 (7), b = 8.877 (3),c = 19.592 (9) A, Z = 8, V = 3979.2 A 3. The Cu Ka intensity data consisted of 1005 unique reflections. Final R -- 14.5%. This nucleotide shows no unusual conformational features. The uracil base has an anti conformation about the glycosidic bond (tpo o = 44.4°). The furanose ring conformation is C(2')-endo,gauchegauche with tpo o = -75.5 ° and ~Poc = 496°.

Structure of disodium deoxyuridine 5'-phosphate pentahydrate

Disodium deoxyuridine 5'-nhosDhate pentahvdrate, Na2(C9H l INEOsP). 5 H20, Call 11N208 P2-. 2Na +. 5 H20, crystallizes in the monoclinic space group P2: with a = 7.250 (4), b = 35.45 (2), c = 7.132 (4)/~, fl = 102.2 (4) °, Z = 4. The Cu Ka intensity data were collected photographically and estimated visually. The structure was obtained by the minimum-function method and difference syntheses and refined to an R of 0.089. In both molecules the uracil base has an anti conformation (2cN = 57.1 and 59.9 °) with respect to the sugar. The deoxyribose moiety of molecule B shows a typical C(l')-exo puckering, with C(I') displaced by 0.52 /k from the best plane. The furanose ring conformation of molecule A can be described as C(2')-endo,C(l')-exo. Both the molecules have an unusual trans-gauche conformation about the exocyclic C(4')-C(5') bond with (~0oo = 171.1, 172.2°; ~0oc = -64.7, -65.9°).

Raman spectral studies of nucleic acids. XVI. Structures of polyribocytidylic acid in aqueous solution.

AbstractRaman spectra of polyribocytidylic acid show the formation of an ordered single‐stranded structure [poly(rC)] at neutral pH and an ordered double‐stranded structure containing hemiprotonated bases [poly(rC)·poly(rC+)] in the range 5.5 > pH > 3.7. Below 40°C, poly(rC) contains stacked bases and a backbone geometry of the A‐type, both of which are gradually eliminated by increasing the temperature to 90°C. Below 80°C, poly(rC)·poly(rC+) contains bases which are hydrogen bonded and stacked and a backbone geometry also of the A‐type. In this structure the bases of each strand are shown to be structurally identical, i.e., hemiprotonated, and therefore distinct from both neutral and protonated cytosines. Infrared and Raman spectra indicate the existence of a center of symmetry with respect to the paired cytosine residues, which suggests that the additional proton per base pair is shared equally by the two hydrogen‐bonded bases. Denaturation of poly(rC)·poly(rC+) occurs cooperatively (tm ≈ 80°C) with elimination of base stacking, base pairing, and the A‐helix geometry. Each of the separated strands of the denatured complex is shown to contain comparable amounts of both neutral and protonated cytosines, most likely in alternating sequence [poly(rC, rC+)]. In both poly(rC, rC+) and poly(rC), at 90°C, the backbones do not exhibit the phosphodiester Raman frequencies characteristic of other disordered polyribonucleotide chains. This is interpreted to mean that the single strands, though devoid of base stacking and A‐type structure, contain uniformly ordered backbones of a specific type. Fully protonated poly(rC+), on the other hand, forms no ordered structure and may be characterized as a disordered (random chain) polynucleotide at all temperatures. Several Raman lines of poly(rC) are absent from the spectrum of poly(rC)·poly(rC+) and vice versa. These frequencies, assigned mainly to vibrations of the ribose groups, suggest that the furanose ring conformations are different in the single‐stranded and double‐stranded structures of polyribocytidylic acid. Several other Raman group frequencies have been identified and correlated with the polymer secondary structures.

Determination of the molecular conformation of beta-D-O2,2'-cyclouridine in aqueous solution by proton magnetic resonance spectroscopy.

AbstractThe solution conformation of β‐D‐O2,2′‐cyclouridine has been determined at 27 and 88°C in D2O by proton magnetic resonance spectroscopy. The conformation is described in terms of a fixed syn‐like sugar‐base torsional angle, a type S furanose ring conformation (similar to 2′‐endo), and a temperature‐dependent exocyclic C(4)′–C(5′) rotamer population containing approximately 50% of the gauche‐gauche form at 27°C. β‐D‐O2,2′‐Cyclouridine 5′‐phosphate likewise possesses a type S furanose ring conformation.

The dimensions and shapes of the furanose rings in nucleic acids.

A survey was made of the geometry of furanose rings in beta-nucleotides and beta-nucleosides (as monomers related to nucleic acids) for which structures have been determined by X-ray crystallography. Mean values, and estimated standard deviations from them, were calculated for bond-lengths, bond-angles and conformation-angles. For parameters with values dependent on ring-puckering, separate calculations were made for each ring type. (The rings are puckered in one of three conformations: C-2- or C-3-endo or C-3-exo; C-2-exo has not been observed.) The results were used to compute standard furanose rings with C-2-endo, C-3-endo and C-3-exo conformations for use in nucleic acid molecular model-building. The survey also showed that the only other conformation-angle in nucleotides dependent on the furanose ring conformation corresponds to the relative orientation of the purine (or pyrimidine) base and the ring.

Optimised parameters for A-DNA and B-DNA

Atomic coordinates and other stereochemical parameters are presented for the A and B conformations of DNA. The molecular structures presented have the most probable values of bond-lengths, bond-angles and furanose ring conformations as defined by accurate X-ray crystallographic analyses of relevant monomers. Conformation-angles have values that provide the best (least-squares) fit with the X-ray diffraction data observed from the polymers themselves. The major difference between A- and B-DNA is in the conformation of the furanose ring that is (C3- endo ) for A and (C3- exo ) for B.

Furanose ring conformation in nucleosides and nucleic acids

Furanose ring conformation in nucleosides and nucleic acids

Molecular theory of sweet taste.

THE molecular feature common to the many different sweet tasting compounds has been sought for many years1. For the sugars, it was proposed2–5 that the sweet unit is the glycol group, and that intensity of sweetness varied inversely with the degree to which glycol OH groups appear to be intramolecularly hydrogen bonded. It is now apparent that vicinal OH groups in the glycol unit need to be approximately gauche, or in a staggered conformation. Vicinal OH groups which are in the anti conformation apparently are too far apart to cause sweet taste. Glycol OH groups which are eclipsed probably participate in an intramolecular hydrogen bond which competitively inhibits interaction of glycol with the receptor site. These steric features of sweet and non-sweet sugar glycol units are shown in perspective in Fig. 1. Glycol conformational parameters, and the gross conformation of pyranose and furanose rings, have been used to explain the varying sweetness of the sugars2–5.

SUCROSE: PRECISE DETERMINATION OF CRYSTAL AND MOLECULAR STRUCTURE BY NEUTRON DIFFRACTION.

This analysis provides the first precise molecular parameters for sucrose. All hydrogen atoms are included. Carbon-carbon distances are 1.51 1.53 A; carbon-oxygen 1.40 to 1.44 A; carbon-hydrogen 1.08 to 1.11 A; oxygen-hydrogen 0.94 to 0.99 A. The furanose ring conformation differs from that in sucrose sodium bromide dihydrate. Hydrogen bonds (two of them intramolecular) utilize every hydroxyl group except one.