Ribose Molecules Research Articles

Ionization of glucose and ribose molecules by electron impact

Ionization of glucose and ribose molecules by electron impact

The Properties of Biomaterials Hidden in the Spaces of Higher Dimension

The influence of the higher dimension of biomolecules on processes in biomaterials is investigated. It has been proved that the optical activity of organic compounds is a consequence of the higher dimensionality of molecules in solution, and not a consequence of the three-dimensional shape of solid crystals, as Pasteur suggested. It is shown that glucose and ribose molecules have dimensions of 15 and 12, respectively. Helical chains of glucose molecules are characterized by the rotation of molecules in perpendicular planes in the opposite directions. A hidden order of interaction of nucleic acids in a space of higher dimension was discovered, leading to a one-to-one correspondence between the number of pair of bound nitrogenous based and the number of amino acids.

Ribosylation induced structural changes in Bovine Serum Albumin: understanding high dietary sugar induced protein aggregation and amyloid formation

Non-enzymatic glycation of proteins is believed to be the root cause of high dietary sugar associated pathophysiological maladies. We investigated the structural changes in protein during progression of glycation using ribosylated Bovine Serum Albumin (BSA). Non enzymatic attachment of about 45 ribose molecules to BSA resulted in gradual reduction of hydrophobicity and aggregation as indicated by red-shifted tryptophan fluorescence, reduced ANS binding and lower anisotropy of FITC-conjugated protein. Parallely, there was a significant decrease of alpha helicity as revealed by Circular Dichroism (CD) and Fourier transformed-Infra Red (FT-IR) spectra. The glycated proteins assumed compact globular structures with enhanced Thioflavin-T binding resembling amyloids. The gross structural transition affected by ribosylation led to enhanced thermostability as indicated by melting temperature and Transmission Electron Microscopy. At a later stage of glycation, the glycated proteins developed non-specific aggregates with increase in size and loss of amyloidogenic behaviour. A parallel non-glycated control incubated under similar conditions indicated that amyloid formation and associated changes were specific for ribosylation and not driven by thermal denaturation due to incubation at 37 °C. Functionality of the glycated protein was significantly altered as probed by Isothermal Titration Calorimetry using polyphenols as substrates. The studies demonstrated that glycation driven globular amyloids form and persist as transient intermediates during formation of misfolded glycated adducts. To the best of our knowledge, the present study is the first systematic attempt to understand glycation associated changes in a protein and provides important insights towards designing therapeutics for arresting dietary sugar induced amyloid formation.

Origin of Coding RNA from Random-Sequence RNA.

D-ribose and D-arabinose differ only by the steric orientation of their C2-OH groups. The initial reactions and emergence of RNA depended on the position, reactivity, and flexibility of the C2-OH moiety in the ribose molecule. The steric relationship of the C2- and C3-OH groups favored the selection of ribose, ribonucleotide, and RNA synthesis and excluded the possibility of xenonucleic acid-based life on Earth. This brief review provides a hypothesis based on the absence of nucleotides and enzymes under prebiotic conditions and on the polymerization of ribose 5-phosphate units leading to the polarized formation of the ribose-phosphate backbone. The strong covalent bond formation in the sugar-phosphate backbone was followed by the somewhat less reactive interaction between ribose and nucleobase and supplemented by even weaker hydrogen-bonded and stacking interactions. This hypothesis proposes a scheme how prebiotic random-sequence RNA was formed under abiotic conditions and hydrolyzed to oligomers and nucleotides. The term random-sequence prebiotic RNA refers to nucleobases attached randomly to the ribose-phosphate backbone and not to cellular RNA sequences as proteins and cells did not probably exist at the time of abiotic RNA formation. It is hypothesized that RNA generated under abiotic conditions containing random nucleobases was hydrolyzed to nucleotides that served as a pool for the selected synthesis of genetic RNA.

The Mechanism of Decreased IgG/IgE-Binding of Ovalbumin by Preheating Treatment Combined with Glycation Identified by Liquid Chromatography and High-Resolution Mass Spectrometry.

Ovalbumin is one of the most important sensitizing ingredients in allergens of egg albumin, which restricts the application of egg in the field of food processing. Previous research has indicated that glycation could cause the protein to partially expand, which may bring about the destruction of the structural IgG and IgE epitopes and induce the decline of the IgG- and IgE-binding ability of ovalbumin. In this research, the effect of a preheating treatment integrated with glycation on the IgG- and IgE-binding capability and the conformation changes of ovalbumin was studied by detecting the glycated sites and the values of degree of substitution per peptide (DSP) by liquid chromatography and high-resolution mass spectrometry (LC-HRMS). Interestingly, we found that a glycation site (K227) attached by two ribose molecules was detected in glycated ovalbumin with preheating treatment. In addition, a new glycation site (K323) appeared in G-60. The results displayed that preheating treament could strengthen the changes in the secondary and tertiary structure of ovalbumin by enhancing glycation and further reduce the IgG/IgE-binding ability by integrating with glycation because of the cover of IgG and IgE epitopes. Therefore, preheating treatment integrated with glycation may offer a way for ovalbumin to reduce sensitization.

Mechanisms of Bacterial ABC Importers: Lessons from Structural and Functional Studies of the Ribose Transporter

Bacterial ATP-Binding Cassette (ABC) transporters are vital for the uptake of nutrients, including sugars, amino acids, and trace metals. Recent studies have identified two types of importers (Class I and II) based on mechanistic and structural differences. The ribose transporter, RbsABC, is a tripartite ABC importer consisting of a cytoplasmic ABC protein with fused nucleotide-binding domains (NBD), a transmembrane domain (TMD) homodimer, RbsC, and a periplasmic substrate binding protein (SBP), RbsB. However, RbsABC is divergent from canonical importers in the fused ATP-binding cassette, which contains both a consensus and degenerate NBD. This organization is observed in eukaryotic ABC exporters, but is thus far unique among characterized bacterial importers. Despite the asymmetry in the NBDs, significant conformational changes are observed in RbsB during transport based on distance measurements from EPR spectroscopy experiments. These changes are driven by the hydrolysis of ATP, providing a pathway for ribose release from RbsB and subsequent transfer to the cytoplasm. Biochemical and EPR experiments also demonstrate that the association between RbsA and RbsC is sensitive to the availability of nucleotide and stimulates ATP hydrolysis in RbsA, providing tight regulation of the catalytic cycle. Finally, it appears a single consensus ATPase site provides ATP hydrolysis to fuel transport, with rescue mutations failing to restore full activity in the degenerate site. EPR experiments suggest an asymmetric closure of the NBDs in response to magnesium and ATP availability. Whether this proposed opening and closing at a single NBD is sufficient to drive transport of a single ribose molecule is currently unknown. The combined observations suggest RbsABC functions by a mechanism distinct from the well-characterized ABC importers for maltose and vitamin B12. Furthermore, RbsABC may provide a key evolutionary link between bacterial and eukaryotic transporters.

Conformational and H-bonding preferences for facile racemate crystallization of ribose.

Recalcitrant crystallization and syrup formation are frequent features of natural sugars. This is the case of D-ribose, yielding low-quality crystals of mixed α- and β-pyranose anomers. However, large crystals of DL-ribose can be grown easily. The crystal structures of stable D-ribose forms I and II as well as DL-form II have been analyzed in terms of their compatibility with the molecular aggregation. The comparison of the potential energy of all conformers and their OH···O hydrogen-bonding patterns is consistent with the preferential racemate crystallization in terms of departures from the optimized isolated ribose molecule and its directional interactions. This analysis is aimed at rationalizing the interplay between the molecular structure and spontaneous crystallization of chiral compounds.

Nucleolar integrity is required for the maintenance of long-term synaptic plasticity.

Long-term memory (LTM) formation requires new protein synthesis and new gene expression. Based on our work in Aplysia, we hypothesized that the rRNA genes, stimulation-dependent targets of the enzyme Poly(ADP-ribose) polymerase-1 (PARP-1), are primary effectors of the activity-dependent changes in synaptic function that maintain synaptic plasticity and memory. Using electrophysiology, immunohistochemistry, pharmacology and molecular biology techniques, we show here, for the first time, that the maintenance of forskolin-induced late-phase long-term potentiation (L-LTP) in mouse hippocampal slices requires nucleolar integrity and the expression of new rRNAs. The activity-dependent upregulation of rRNA, as well as L-LTP expression, are poly(ADP-ribosyl)ation (PAR) dependent and accompanied by an increase in nuclear PARP-1 and Poly(ADP) ribose molecules (pADPr) after forskolin stimulation. The upregulation of PARP-1 and pADPr is regulated by Protein kinase A (PKA) and extracellular signal-regulated kinase (ERK)—two kinases strongly associated with long-term plasticity and learning and memory. Selective inhibition of RNA Polymerase I (Pol I), responsible for the synthesis of precursor rRNA, results in the segmentation of nucleoli, the exclusion of PARP-1 from functional nucleolar compartments and disrupted L-LTP maintenance. Taken as a whole, these results suggest that new rRNAs (28S, 18S, and 5.8S ribosomal components)—hence, new ribosomes and nucleoli integrity—are required for the maintenance of long-term synaptic plasticity. This provides a mechanistic link between stimulation-dependent gene expression and the new protein synthesis known to be required for memory consolidation.

Relaxation of the T1 excited state of 2-thiothymine, its riboside and deoxyriboside-enhanced nonradiative decay rate induced by sugar substituent

Abstract UV absorption, circular dichroism and emission spectroscopy as well as nanosecond and femtosecond transient absorption measurements were used to characterize the excited states of 2-thiothymine (2TT), its riboside (2TTR) and deoxyriboside (2TTD) in acetonitrile (ACN) solution. The lowest triplet state (T1) could be observed exclusively in the experiments. Upon excitation to higher singlet states (λexc = 266 nm), the T1 (ππ*) states of the investigated compounds were formed on an ultrafast time scale (kT ≥ 3 × 1012 s−1) with an efficiency approaching unity (ϕT = 0.9 ± 0.1). These T1 states were characterized by their intrinsic lifetimes ( τ T 0 ) and rate constants of self-quenching (kSQ), phosphorescence (kP), and nonradiative processes (∑kNR). In the series of compounds studied only 2TT exhibited a weak room-temperature phosphorescence, and the spectrum of this 2TT emission was recorded for the first time. In the absence of self quenching, nonradiative processes (NR) are the dominant (ϕNR ∼ 0.9) channel of the decay of 2TT and its nucleosides in their T1 states. Despite the chromophore being the same in all of the compounds studied, the decay dynamics of the nucleosides’ T1 states differed considerably from that of the T1 state of 2TT. The ∑kNR values determined for the derivatives containing a ribosyl (in 2TTR) or a deoxyribosyl (in 2TTD) substituent in the position α to the thiocarbonyl group were an order of magnitude larger, and as a consequence, the lifetimes ( τ T 0 ) shorter (by factor of 14 and 22 for 2TTD and 2TTR, respectively) as compared to 2TT. The reason for the enhanced rate of nonradiative decay in the nucleosides is discussed based on the results obtained from additional experiments including the determination of the T1 lifetime for the deuterated derivative of 2TTR and the intermolecular quenching of 2TT by ribose molecules. The factors which might be responsible for this substituent effect (on the nonradiative decay) such as an intramolecular or an intermolecular H bond formation involving sugar OH groups as well as a reversible H abstraction from the sugar α-substituent in the nucleosides appear to be not important.

Photofragmentation of 2‐Deoxy‐D‐Ribose Molecules in the Gas Phase

We have measured the synchrotron-induced photofragmentation of isolated 2-deoxy-D-ribose molecules (C(5)H(10)O(4)) at four photon energies, namely, 23.0, 15.7, 14.6, and 13.8 eV. At all photon energies above the molecule's ionization threshold we observe the formation of a large variety of molecular cation fragments, including CH(3) (+), OH(+), H(3)O(+), C(2)H(3) (+), C(2)H(4) (+), CH(x)O(+) (x=1,2,3), C(2)H(x)O(+) (x=1-5), C(3)H(x)O(+) (x=3-5), C(2)H(4)O(2) (+), C(3)H(x)O(2) (+) (x=1,2,4-6), C(4)H(5)O(2) (+), C(4)H(x)O(3) (+) (x=6,7), C(5)H(7)O(3) (+), and C(5)H(8)O(3) (+). The formation of these fragments shows a strong propensity of the DNA sugar to dissociate upon absorption of vacuum ultraviolet photons. The yields of particular fragments at various excitation photon energies in the range between 10 and 28 eV are also measured and their appearance thresholds determined. At all photon energies, the most intense relative yield is recorded for the m/q=57 fragment (C(3)H(5)O(+)), whereas a general intensity decrease is observed for all other fragments- relative to the m/q=57 fragment-with decreasing excitation energy. Thus, bond cleavage depends on the photon energy deposited in the molecule. All fragments up to m/q=75 are observed at all photon energies above their respective threshold values. Most notably, several fragmentation products, for example, CH(3) (+), H(3)O(+), C(2)H(4) (+), CH(3)O(+), and C(2)H(5)O(+), involve significant bond rearrangements and nuclear motion during the dissociation time. Multibond fragmentation of the sugar moiety in the sugar-phosphate backbone of DNA results in complex strand lesions and, most likely, in subsequent reactions of the neutral or charged fragments with the surrounding DNA molecules.

Targeted Skipping of a Single Exon Harboring a Premature Termination Codon Mutation: Implications and Potential for Gene Correction Therapy for Selective Dystrophic Epidermolysis Bullosa Patients

This study examined the feasibility of antisense oligoribonucleotide (AON) therapy for dystrophic epidermolysis bullosa (DEB). AON was designed to induce skipping of a targeted exon containing a premature termination codon mutation, resulting in restoration of the open reading frame. We targeted exon 70 of COL7A1, as a recurrent mutation 5818delC in Japanese DEB patients was localized to exon 70. We found that one AON induced effective skipping of normal exon 70 containing 16 amino acids. Attachment and migration analyses showed that recombinant collagen without contribution of exon 70 was similar in effect to normal type VII collagen. Next, we synthesized mutation-specific AON by deleting cytosine at 5818. Introduction of this AON into DEB keratinocytes harboring 5818delC showed that the AON induced skipping of exon 70 in the abnormal 5818delC allele. Furthermore, 6.2% of DEB keratinocytes started to express type VII collagen in vitro after application of the mutation-specific AON. Injection of the AON into rat model grafted with DEB keratinocytes and fibroblasts induced a low amount of type VII collagen expression. We conclude that skipping of targeted exons using mutation-specific AON may show potential for future gene therapy for DEB patients.

Conformational topology of ribose: A computational study

This work concerns the theoretical study of the configurational topology of the ribose molecule. MP2/6-31G** geometry optimizations of the system have yielded several structures corresponding to local minima on the ground-state potential energy surface and the lowest energy configuration was identified. The stability of a few lowest lying conformations has been recalculated at the CCSD(T)/6-31G** level of theory.

Quantification of ion-induced molecular fragmentation of isolated 2-deoxy-d-ribose molecules

Recent experiments on low energy ion-induced damage to DNA building blocks indicate that ion induced DNA damage is dominated by deoxyribose disintegration (Phys. Rev. Lett., 2005, 95, 153201). We have studied interactions of keV H+ and He(q+) with isolated deoxyribose molecules by means of high resolution time-of-flight spectrometry. Extensive statistical fragmentation of the molecules is observed. The fragment distribution is found to follow a power law dependence. The exponent can be used to characterize and quantify the molecular damage.

Simple Ethers as Models of Sugar Molecules in Calculations of Vertical Excitation Energies of DNA and RNA Nucleosides

The ribose and deoxyribose molecules of RNA and DNA nucleosides are substituted with simple model compounds 1-methoxy-2-ethanol and 1-methoxypropane to mimic the effect of binding to sugars on the vertical excitation energies of purine and pyrimidine bases. The (R)-1-methoxy-2-ethanol, CH(3)OC*HCH(2)OH, for model ribose nucleosides and (R)-1-methoxypropane, CH(3)OC*HC(2)H(5), for model deoxyribose nucleosides have minimal structural characteristics of ribose and deoxyribose molecules when attached to nucleic acid purine and pyrimidine bases. The bases are attached to the C1 carbon atom designated by the asterisk. The vertical excitation energies of these model nucleosides are calculated with the time-dependent density functional theory method at the B3LYP level with 6-311++G(d,p) and aug-cc-pVDZ basis sets. The attachment of the ether molecules qualitatively and quantitatively modifies the excited state energy levels of the model nucleosides when compared to the free bases. These changes can affect the deexcitation mechanisms for photoexcited nucleosides.

Sugar complexation with calcium ion. Crystal structure and FT-IR study of a hydrated calcium chloride complex of d-ribose

The single crystal structure of CaCl 2·C 5H 10O 5·3H 2O was determined with M r=315.16, a=7.537(3), b=11.426(5), c=15.309(6) Å, β=90°, V=1318.3(9) Å 3, P2(1)2(1)2(1), Z=2, μ=0.71073 Å and R=0.0398 for 2322 observed reflections. The ribose moiety of the complex exists as a furanose with α- d configuration. All five oxygen atoms of the ribose molecule are involved in calcium binding. Each calcium ion is shared by two such sugar molecules, coordinating through O(1), O(2), O(3) of one molecule and O(4) and O(5) of the other. The C–C, O–H, C–O and C–O–H vibrations are shifted and the relative intensities changed in the complex IR spectrum, corresponding to the changes in bond distances and angles of the sugar structure. All the hydroxyl groups, water molecules and chloride ions are involved in forming an extensive hydrogen-bond network of O–H⋯Cl⋯O–H structure, and the chloride ions play an important role in the crystal packing.

THE EFFECT OF CYTOSINE- AND GUANINE NUCLEOTIDES ON THE ISOLATED FROG HEART.

1. The effect of the cytosine- and guanine nucleotides on hypodynamic frog hearts was investigated. 2. After an ample discussion of our data and those of the literature we concluded: a) that for the positive inotropic effect (second phase) the polyphosphate structure of the nucleotides is important; that it is very probable that a phosphate liberation by rupture of energy rich phosphate bonds forms the base of the inotropic effect; that for the initial effect this phosphate liberation is potentiated by the —6 NH2 group in either the purine or the pyrimidine ring, while this configuration has no effect on the phosphate liberation in the second increase. Therefore it is likely that the initial and the second increase of cardiac contraction are based on two different processes of phosphate liberation; b) that the negative chronotropic effect of adenosine, AMP, ADP and ATP on the heart is based on the —6 NH2 group in the purine ring, which only has an effect if a ribose molecule is linked to the base.

ADENINE DERIVATIVES AND THEIR BIOLOGICAL FUNCTIONS

SummaryAdenine derivatives represent a group of substances of considerable biological interest. Our knowledge of their occurrence in nature, properties and role is derived from both chemical and biological investigations.With regard to chemical structure, they fall into three groups of different complexity: (I) the comparatively simple molecules adenosine, adenylic acid, adenyl pyrophosphoric acid, (2) the intermediate compounds di‐adenosine‐penta‐phosphoric and di‐adenosine‐tetraphosphoric acid, and (3) the dinucleotides cozy‐mase, Warburg's coenzyme, amino‐acid oxidase coenzyme, which apart from adenine possess yet another base (pyridine, alloxazine).Adenosine does not occur in free state in nature. It can be obtained by hydrolysis from yeast nucleic acid. Adenosine is a substance of potent physiological activity, especially on the heart. Deamination of adenosine to inosine (e.g. by enzymes present in many tissues and body fluids) renders this substance phydogically inactive.Adenylic acid (adenine nucleotide) is a general cell constituent. With regard to chemical structure we distinguish between muscle and yeast adenylic acid, the phosphoric group in the former being attached to C5, in the latter to C3, of the ribose molecule. Accordingly these two substances differ in several aspects, both chemical and biological. It is the muscle adenylic structure which is met with in the rest of the higher adenine derivatives.Adenylic acid occurs in tissues and cells in the form of adenyl pyrophosphoric acid and only seldom in free state (heart muscle). The pyrophosphoric group is easily split off, enzymically or by acid hydrolysis. A method is described for quantitative determination of adenyl pyrophosphoric and adenylic acid in biological material.In addition to adenylic and adenyl pyrophosphoric acid there exist other poly‐phosphoric adenine derivatives, such as the di‐adenosine‐pentaphosphoric acid in heart muscle and the di‐adenosine‐tetraphosphoric acid in yeast.Cozymase, diphosphopyridine nucleotide, originally called “coenzyme of alcoholic fermentation”, is a substance of wide distribution in nature. Owing to the presence of the pyridine ring (nicotinic acid amide) in its molecule, it can undergo reversible oxidation and reduction: cozymasezdihydrocozymase. In the enzymic oxido‐reduction systems (dehydrogenases) where it acts as coenzyme it plays the part of a hydrogen carrier, transferring the hydrogen from the substrate to a hydrogen acceptor such as flavoprotein.Warburg's coenzyme, triphosphopyridine nucleotide, was first isolated from red blood cells and later found to occur in many other cells. Structurally it is closely related to cozymase, but it possesses one more phosphoric acid group than cozymase. The mechanism of its action as hydrogen carrier in enzyme systems is identical to that of cozymase, but in purified enzyme preparations these two coen‐zymes cannot replace each other in spite of their close similarity. There is some evidence, however, that cozymase and Warburg's coenzyme are to a certain degree interconvertibIe under the influence of cell extracts.Alloxazine‐adenine nucleotide is a substance of ubiquitous presence in biological material. Originally isolated from heart muscle and kidney as the coenzyme of the amino‐acid oxidase, it was soon found to be essential for other enzymic proteins as well (flavoprotein, xanthine oxidase). Its role as hydrogen carrier is due to the reversible oxidation and reduction of the alloxazine ring.The function of the adenine derivatives in biological processes, e.g. phosphate transfer by the adenylic system and hydrogen transfer by cozymase, is discussed in muscle glycolysis and alcoholic fermentation. Coupling is shown to occur between the phosphorylations and oxido‐reductions in some of the intermediary stages of glycolysis and fermentation.Enzyme systems are quoted in which the two pyridine dinucleotides and the alloxazine dinucleotide act as coenzymes.