Mediation of the A/B-DNA helix transition by G-tracts in the crystal structure of duplex CATGGGCCCATG

The crystal structure of the DNA dodecamer duplex CATGGGCCCATG lies on a structural continuum along the transition between A- and B-DNA. The dodecamer possesses the normal vector plot and inclination values typical of B-DNA, but has the crystal packing, helical twist, groove width, sugar pucker, slide and x-displacement values typical of A-DNA. The structure shows highly ordered water structures, such as a double spine of water molecules against each side of the major groove, stabilizing the GC base pairs in an A-like conformation. The different hydration of GC and AT base pairs provides a physical basis for solvent-dependent facilitation of the A↔B helix transition by GC base pairs. Crystal structures of CATGGGCCCATG and other A/B-DNA intermediates support a ‘slide first, roll later’ mechanism for the B→A helix transition. In the distribution of helical parameters in protein–DNA crystal structures, GpG base steps show A-like properties, reflecting their innate predisposition for the A conformation.     

Sequence-dependent variation in the conformation of DNA

The specificity of action of the enzyme DNAase I on double-stranded DNA polymers of defined sequence has been investigated. The results obtained with the alternating copolymers poly[d(A-T)] · poly[d(A-T)] and poly[d(G-C)] · poly[d(G-C)] support the suggestion of Klug et al. (1979) that regions of double-stranded DNA containing alternating purine-pyrimidine sequences may exist as structural variants of the classical B-form under physiological salt conditions. Digestion of defined oligomers containing alternating dG-dC sequences indicate that these too exist in some “alternating-B” structure in solution under similar conditions. The results obtained with the oligomers also provide a number of insights into the mode of action of DNAase I.In the case of the B-DNA dodecamer d(C-G-C-G-A-A-T-T-C-G-C-G), for which the crystal structure has been solved (Dickerson &; Drew, 1981), there is a very good correlation between the sites of rapid DNAase I cutting and positions of high local helical twist.     

Amide protein exchange and surface conformation of the basic pancreatic trypsin inhibitor in solution. Studies with two-dimensional nuclear magnetic resonance

Dickerson and his colleagues have described the structure of the DNA dodecamer C-G-C-G-A-A-T-T-C-G-C-G in the B form at a level that shows clearly several aspects of some base sequence-dependent departures from the ideal, regular helical structure of B-DNA. I argue that the detailed conformation is a consequence of simple steric repulsive forces between purine bases in consecutive base-pairs but on opposite backbones. These repulsions are a consequence of the “propeller twist” of the base-pairs, together with the larger size of the purine bases, and they may occur in either the major or the minor groove. The argument is conducted in terms of the structural mechanics of a deformable elastic system. These repulsive forces between the base-pairs are resisted by stresses in the helical backbones, which may be studied quantitatively via the variation in torsion angles δ along the backbones, at the points where the sugar rings are connected. There is also a correlation between the cross-chain purine repulsions and the perturbations in helical twist angle between successive base-pairs. The work suggests some comments on the proposed “alternating B” form, the Z form and the A form of DNA.     

Solution structure of the dodecamer d-(CATGGGCC-CATG)2 is B-DNA. Experimental and molecular dynamics study

The DNA duplex d-(CATGGGCCCATG)2 has been studied in solution by FTIR, NMR and CD. The experimental approaches have been complemented by series of large-scale unrestrained molecular dynamics simulation with explicit inclusion of solvent and counterions. Typical proton-proton distances extracted from the NMR spectra and the CD spectra are completely in agreement with slightly modified B-DNA. By molecular dynamics simulation, starting from A-type sugar pucker, a spontaneous repuckering to B-type sugar pucker was observed. Both experimental and theoretical approaches suggest for the dodecamer d-(CATGGGCCCATG)2 under solution conditions puckering of all 2'-deoxyribose residues in the south conformation (mostly C2'-endo) and can exclude significant population of sugars in the north conformation (C3'-endo). NMR, FTIR and CD data are in agreement with a B-form of the dodecamer in solution. Furthermore, the duplex shows a cooperative B-A transition in solution induced by addition of trifluorethanol. This contrasts a recently published crystal structure of the same oligonucleotide found as an intermediate between B- and A-DNA where 23 out of 24 sugar residues were reported to adopt the north (N-type) conformation (C3'-endo) like in A-DNA (Ng, H. L., Kopka, M. L. and Dickerson, R. E., Proc. Natl. Acad. Sci. U S A 97, 2035-2039 (2000)). The simulated structures resemble standard B-DNA. They nevertheless show a moderate shift towards A-type stacking similar to that seen in the crystal, despite the striking difference in sugar puckers between the MD and X-ray structures. This is in agreement with preceding MD reports noticing special stacking features of G-tracts exhibiting a tendency towards the A-type stacking supported by the CD spectra also reflecting the G-tract stacking. MD simulations reveal several noticeable local conformational variations, such as redistribution of helical twist and base pair roll between the central GpC steps and the adjacent G-tract segments, as well as a substantial helical twist variability in the CpA(TpG) steps combined with a large positive base pair roll. These local variations are rather different from those seen in the crystal.     

Determination of reduction potential of an engineered Cu<Subscript>A</Subscript> azurin by cyclic voltammetry and spectrochemical titrations

The reduction potentials of an engineered Cu_A azurin in its native and thermally denatured states have been determined using cyclic voltammetry and spectrochemical titrations. Using a 4,4-dipyridyl disulfide modified gold electrode, the reduction potentials of native and thermally denatured Cu_A azurin are the same within the experimental error (422±5 and 425±5 mV vs. NHE, respectively, in 50 mM ammonium acetate buffer, pH 5.1, 300 mM NaCl, 25 °C), indicating that the potential is that of a nonnative state. In contrast, using a didodecyldimethylammonium bromide (DDAB) film-pyrolytic graphite edge (PGE) electrode, the reduction potentials of native and thermally denatured Cu_A azurin have been determined to be 271±7 mV (50 mM ammonium acetate buffer, pH 5.1, 4 °C) and 420±1 mV (50 mM ammonium acetate buffer, pH 5.1, 25 °C), respectively. Spectroscopic redox titration using [Ru(NH₃)₅Py]²⁺ resulted in a reduction potential (254±4 mV) (50 mM ammonium acetate buffer, pH 5.1, 4 °C) similar to the value obtained using the DDAB film-PGE electrochemical method. Complete reoxidation of [Ru(NH₃)₅Py]²⁺-reduced Cu_A azurin is also consistent with the conclusion that this spectrochemical titration method using [Ru(NH₃)₅Py]²⁺ measures the reduction potential of native Cu_A azurin.Abbreviations CcO cytochrome c oxidase - N₂OR nitrous oxide reductase - ET electron transfer - CV cyclic voltammetry - NHE normal hydrogen electrode - DDAB didodecyldimethylammonium bromide - PGE pyrolytic graphite edge     

An unusual feature of end-substituted model carbon (6,0) nanotubes

We have examined the effects of substituents on the computed electrostatic potentials V_S(r) and average local ionization energies on the surfaces of model carbon nanotubes of the types (5,5), (6,1) and (6,0). For the (5,5) and the (6,1), the effects upon both V_S(r) and of substituting a hydroxyl group at one end are primarily localized to that part of the system. For the (6,0) tube, however, a remarkable change is observed over its entire length, with V_S(r) showing a marked gradation from strongly positive at the substituted end to strongly negative at the other; correspondingly goes from higher to lower values. Replacing OH by another resonance- donor, NH₂, produces similar results in the (6,0) system, while the resonance withdrawing NO₂ does the opposite, but in equally striking fashion. We explain these observations by noting that the arrangement of the C–C bonds in the (6,0) tube facilitates charge delocalization over the full length and entire surface of the tube. Substituting NH₂ and NO₂ at opposite ends of the (6,0) tube greatly strengthens the gradations in both V_S(r) and The first hyperpolarizability of this system was found to be nine times that of para-nitroaniline, suggesting possible nonlinear optical applications.Figure HF/STO-5G electrostatic potential on outer surface of open (6,0) C₇₂H₁₀NH₂NO₂. The nitro group is at the right end of the tube, the amino group at the left. In eV: purple is less than 14, blue is between 14 and 15, green is between 15 and 16.5, yellow is between 16.5 and 17.5, and red is more than 17.5.      

Assignments of 31P NMR resonances in oligodeoxyribonucleotides: origin of sequence-specific variations in the deoxyribose phosphate backbone conformation and the 31P chemical shifts of double-helical nucleic acids

It is now possible to unambiguously assign all 31P resonances in the 31P NMR spectra of oligonucleotides by either two-dimensional NMR techniques or site-specific 17O labeling of the phosphoryl groups. Assignment of 31P signals in tetradecamer duplexes, (dTGTGAGCGCTCACA)2, (dTAT-GAGCGCTCATA)2, (dTCTGAGCGCTCAGA)2, and (dTGTGTGCGCACACA)2, and the dodecamer duplex d(CGTGAATTCGCG)2 containing one base-pair mismatch, combined with additional assignments in the literature, has allowed an analysis of the origin of the sequence-specific variation in 31P chemical shifts of DNA. The 31P chemical shifts of duplex B-DNA phosphates correlate reasonably well with some aspects of the Dickerson/Calladine sum function for variation in the helical twist of the oligonucleotides. Correlations between experimentally measured P-O and C-O torsional angles and results from molecular mechanics energy minimization calculations show that these results are consistent with the hypothesis that sequence-specific variations in 31P chemical shifts are attributable to sequence-specific changes in the deoxyribose phosphate backbone. The major structural variation responsible for these 31P shift perturbations appears to be P-O and C-O backbone torsional angles which respond to changes in the local helical structure. Furthermore, 31P chemical shifts and JH3'-P coupling constants both indicate that these backbone torsional angle variations are more permissive at the ends of the double helix than in the middle. Thus 31P NMR spectroscopy and molecular mechanics energy minimization calculations appear to be able to support sequence-specific structural variations along the backbone of the DNA in solution.     

Cold tolerance in nematodes

Summary The nematodesTrichostrongylus colubriformis (J3),Ditylenchus dipsaci (J4) andPanagrellus silusae (adults) are freezing-susceptible but can avoid freezing by supercooling. Their mean supercooling points were –30.0±0.7°C forT. colubriformis, –21.7±0.7°C forD. dipsaci and –20.7±0.84°C forP. silusae. T. colubriformis andD. dipsaci could prevent seeding by external ice butP. silusae could not. The glycerol concentrations of these nematodes are considered to be too low to have a significant antifreeze effect.Abbreviations J3 3rd-stage juvenile - J4 4th stage juvenile - SEM standard error of the mean - T ₅₀ 50% survival temperature     

Determining the binding mode and binding affinity constant of tyrosine kinase inhibitor PD153035 to DNA using optical tweezers

Accurately predicting binding affinity constant (K_A) is highly required to determine the binding energetics of the driving forces in drug–DNA interactions. Recently, PD153035, brominated anilinoquinazoline, has been reported to be not only a highly selective inhibitor of epidermal growth factor receptor but also a DNA intercalator. Here, we use a dual-trap optical tweezers to determining K_A for PD153035, where K_A is determined from the changes in B-form contour length (L) of PD153035–DNA complex. Here, L is fitted using a modified wormlike chain model. We found that a noticeable increment in L in 1 mM sodium cacodylate was exhibited. Furthermore, our results showed that K_A = 1.18(±0.09) × 10⁴ (1/M) at 23 ± 0.5 °C and the minimum distance between adjacent bound PD153035 ≈ 11 bp. We anticipate that by using this approach we can determine the complete thermodynamic profiles due to the presence of DNA intercalators.     

Intracellular activity of morphologically identified neurons of the grass frog's optic tectum in response to moving configurational visual stimuli

Summary In the grass frogRana temporaria, various classes of tectal neurons were identified by means of intracellular recording and iontophoretic staining using potassium-citrate/Co³⁺-lysine-filled micropipettes, which have been defined previously by extracellular recording methods. Class T5(1) neurons had receptive fields (RF) of 33°±5° diameter. In response to a moving 8°×8° square (S), a 2°×16° worm-like (W), or a 16°×2° antiworm-like (A) moving stripe, these cells showed excitatory postsynaptic potentials (EPSPs) and spikes which were interrupted occasionally by small inhibitory postsynaptic potentials (IPSPs). The excitatory responses (R) were strongest towards the square (R_S) and less to the worm (R_W). For the antiworm (R_A) the responses were smallest or equal to the worm stimulus yielding the relationship R_S>R_WR_A. Some of these cells were identified as pear-shaped or large ganglionic neurons, whose somata were located in the tectal cell layer 8. The somata of other large ganglionic neurons were found in layer 7 and the somata of other pear-shaped neurons at the top of layer 6, both displaying T5(1) properties. Class T5(2) neurons (RF=34°±3°) responded with large EPSPs and spikes, often interrupted by small IPSPs, when their RF was traversed by the square stimulus. The excitatory activity was somewhat less to the worm stimulus, whereas no activity at all, or only IPSPs, were recorded in response to the antiworm-stimulus; thus yielding the relationship for the excitatory activity R_S>R_W>R_A 0. Such a cell was identified as pyramidal neuron; the soma was located at the top of layer 6, with the long axon travelling into layer 7 to the medulla oblongata. Class T5(3) neurons (RF=29°±6°) showing EPSPs and spikes according to the relationship R_S>R_A>R_W have been identified as large ganglionic neurons. Their somata were located in layer 8. Class T5(4) neurons (RF=24±7°) responded only to the square stimulus with EPSPs and spikes, sometimes interrupted by IPSPs and yielding the relationship R_S>R_AR_W0. The somata of these large ganglionic or pear-shaped neurons were located in layer 8. Class T1(1) neurons (RF=30°–40°) were most responsive to stimuli moving at a relatively long distance in the binocular visual field, and have been identified as pear-shaped neurons. Their somata were located in layer 6.Further neurons are described and morphologically identified which have not yet been classified by extracellular recording methods. For example,IPSP neurons (RF=20°–30°) responded (R) with IPSPs only according to the relationship R_S>R_A R_W. The somata of these pear-shaped neurons were located in layer 6.The properties of tectal cells in response to electrical stimulation of the optic tract and to brisk changes of diffuse illumination suggest certain neuronal connectivity patterns. The results support the idea ofintegrative functional units (assemblies) of connected cells which are involved in various perceptual processes, such as configurational prey selection expressed by T5(2) prey-selective neurons.Abbreviations A antiworm-like 16°×2° stripe stimulus with long axis perpendicular to the direction of movement - W wormlike 2°×16° stripe stimulus with long axis oriented parallel to the direction of movement - S square 8°×8° moving stimulus - ERF excitatory receptive field - IRF inhibitory receptive field - RF receptive field - EPSP excitatory postsynaptic potential - IPSP inhibitory postsynaptic potential     

Quantitative structure-activity relationship by CoMFA for cyclic urea and nonpeptide-cyclic cyanoguanidine derivatives on wild type and mutant HIV-1 protease

Abstact 3D-QSAR studies using the Comparative Molecular Field Analysis (CoMFA) methodology were conducted to predict the inhibition constants, K_i, and the inhibitor concentrations, IC₉₀ of 127 symmetrical and unsymmetrical cyclic urea and cyclic cyanoguanidine derivatives containing different substituent groups such as: benzyl, isopropyl, 4-hydroxybenzyl, ketone, oxime, pyrazole, imidazole, triazole and having anti-HIV-1 protease activities. A significant cross-validated correlation coefficient (q²) of 0.63 and a fitted correlation coefficient r² of 0.70 were obtained, indicating that the models can predict the anti-protease activity from poorly to highly active compounds reliably. The best predictions were obtained for: XV643 (predicted log 1/K_i=9.86), a 3,5-dimethoxy-benzyl cyclic urea derivate (molec60, predicted log 1/K_i=8.57) and a benzyl cyclic urea derivate (molec 61, predicted log 1/IC₉₀=6.87). Using the CoMFA method, we also predicted the biological activity of 14 cyclic urea derivatives that inhibit the HIV-1 protease mutants V82A, V82I and V82F. The predicted biological activities of the: (i) XNO63 (inhibitory activity on the mutant HIV-1 PR V82A), (ii) SB570 (inhibiting the mutant HIV-1 PR V82I) and also (iii) XV652 (during the interaction with the mutant HIV-1 PR V82F) were in good agreement with the experimental values.Figure Stereoview of the contour plots of the CoMFA steric and electrostatic fields. The favorable (indicated by blue polyhedra) and unfavorable (represented by red polyhedra) electrostatic areas and also the favorable (shown by green polyhedra) and unfavorable (shown by yellow polyhedra) steric areas formed around the most active molecule, 6a.     

Molecular Dynamics Simulation of 7, 8-dihydro-8-Oxoguanine DNA

Abstract

To elucidate the effect of guanine lesion produced by the oxidative damage on DNA, 1 nanosecond molecular dynamics simulations of native and oxidized DNA were performed. The target DNA molecules are dodecamer duplex d(CGCGAATTCGCG)2 and its derivative duplex d(C₁G₂C₃(8-oxoG)₄A₅A₆T₇T₈C₉G₁₀C₁₁G₁₂)·d(C₁₃G₁₄C₁₅G₁₆A₁₇A₁₈T₁₉T₂₀C21_G22C₂₃G₂₄), which has one oxidized guanine, 7, 8-dihydro-8-oxoguanine (8-oxoG), at the fourth position. The local structural change due to the lesion of 8-oxoG and the global dynamic structure of the 8-oxoG DNA were studied. It was found that the 8-oxoG DNA remained structurally stable during the simulation due to newly produced hydrogen bonds around the (8-oxoG)₄ residue. However, there were distinguishable differences in structural parameters and dynamic property in the 8-oxoG DNA. The conformation around the (8- oxoG)₄ residue departed from the usual conformation of native DNA and took an unique conformation of ?-ζ in B_II conformation and χ in high anti orientation at the (8-oxoG)₄ residue, and adopted a very low helical twist angle at the C₃:G₂₂—(8-oxoG)₄:C₂₁ step. Further analysis by principal component analysis indicated that the formation of the hydrogen bonds around the (8-oxoG)₄ residue plays a role as a trigger for the conformational transition of the 8-oxoG DNA in the conformational space.     

Prototropic tautomerism of imidazolone in aqueous solution: a density functional approach using the combined discrete/self-consistent reaction field (SCRF) models

A systematic investigation of the proton transfer in the keto-amino/enol tautomerization of imidazolone was undertaken. Calculations in aqueous solution were performed using both combined discrete/self-consistent reaction field (SCRF) and SCRF methods. Complexes containing one to three water molecules around the hydrophilic site of imidazolone were used for the combined discrete/SCRF calculations. The DFT results predict that the barrier height for non-water-assisted intramolecular proton transfer is very high (214.8 kJmol^–1). Hydrogen bonding between imidazolone and the water molecule(s) will dramatically lower the barrier by a concerted multiple proton transfer mechanism. The proton transfer process through a eight-member ring formed by imidazolone and two water molecules is found to be more efficient and the calculated barrier height is ca. 61 kJmol^–1.Figure DFT calculations in aqueous solution predict the H-bonding between imidazolone(IZ) and the water molecule(s) will dramatically lower the tautomeric barrier by a concerted multiple proton transfer mechanism, in which an eight-member ring structure formed by IZ and 2H₂O is found to be more efficient and the barrier is 60.8 kJ mol^–1, much less than 214.8 kJ mol^–1 in the non-water-assisted mechanism.     

Hormonal growth-promotant effects on grain-fed cattle maintained under different environments

Six steers (3/4 Charolais×1/4 Brahman) (mean body weight 314±27 kg) and six spayed heifers (3/5 Shorthorn×2/5 Red Angus) (mean body weight 478±30 kg) were used to determine the effects of climatic conditions and hormone growth promotants (HGP) on respiration rate (RR; breaths/min), pulse rate (beats/min), rectal temperature (RT; °C), and heat production (HP; kJ). Cattle were exposed to the following climatic conditions prior to implantation with a HGP and then again 12 days after implantation: 2 days of thermoneutral conditions (TNL) [21.9±0.9°C ambient temperature (T_A) and 61.7±22.1% relative humidity (RH)] then 2 days of hot conditions [HOT; 29.2±4°C (T_A) and 78.3±13.2% (RH)], then TNL for 3 days and then 2 days of cold conditions [COLD; 17.6±0.9°C (T_A) and 63.4±1.8% (RH); cattle were wet during this treatment]. The HGP implants used were: estrogenic implant (E), trenbolone acetate implant (TBA), or both (ET). Both prior to and following administration of HGP, RRs were lower (P<0.05) on cold days and greater (P<0.05) on hot days compared to TNL. On hot days, RTs, were 0.62°C higher after compared to before implanting. Across all conditions, RTs were >0.5°C greater (P<0.05) for E cattle than for TBA or ET cattle. On cold days, RTs of steers were >0.8°C higher than for the heifers, while under TNL and HOT, RTs of steers were 0.2–0.35°C higher than those of heifers. Prior to implantation, HP per hour and per unit of metabolic body weight was higher (P<0.05) for cattle exposed to hot conditions, when compared to HP on cold days. After implantation, HP was greater (P<0.05) on hot days than on cold days. Under TNL, ET cattle had the lowest HP and greatest feed intake. On hot days, E cattle had the lowest HP, and the highest RT; therefore, if the potential exists for cattle death from heat episodes, the use of either TBA or ET may be preferred. Under cold conditions HP was similar among implant groups.     

Decomposition mechanism of 3-<Emphasis Type="Italic">N</Emphasis>-morpholinosydnonimine (<Emphasis Type="Bold">SIN-1</Emphasis>)—a density functional study on intrinsic structures and reactivities

Selected intrinsic aspects of the mode of action of 3-N-morpholinosydnonimine (SIN-1) and its follow-up products are investigated by means of density functional theory. Besides the well known radical-cationic Feelisch–Schoenafinger pathway, an alternative anionic route via a neutral radical is proposed and included in the study. The individual reaction pathways are followed. Most notably, the overall activation barrier for the cationic route is calculated to be 184.04 kcal mol^–1, while the one for the anionic route is predicted to be more favorable with 14.09 kcal mol^–1.Figure A mere conformational change is predicted by DFT theory to elicit NO ejection from the SIN-1a radical cation, formed after one electron oxidation of the N-nitrosohydrazine SIN-1a.

Organization of rhodopsin molecules in native membranes of rod cells–an old theoretical model compared to new experimental data

It has been shown that rhodopsin forms an oligomer in the shape of long double rows of monomers. Because of the importance of rhodopsin as a template for all G protein-coupled receptors, its dimeric, tetrameric and higher-oligomeric structures also provide a useful pattern for similar structures in GPCRs. New experimental data published recently are discussed in the context of a proposed model of the rhodopsin oligomer 1N3M deposited in the protein data bank. The new rhodopsin structure at 2.2 Å resolution with all residues resolved as well as an electron cryomicroscopy structure from 2D crystals of rhodopsin are in agreement with the 1N3M model. Accommodation of movement of transmembrane helix VI, regarded as a major event during the activation of rhodopsin, in a steady structure of the oligomer is also discussed.Figure Superimposition of the 1U19 (red wire), 1GZM (purple wire) and 1N3M (blue wire) rhodopsin structures. Size of the wires is proportional to thermal factors of backbone C atoms, view parallel to the membrane.      

Diffusion von45Ca,85Sr und32P in Hydroxylapatit

Zusammenfassung Es wurde der Transport von⁴⁵Ca,⁸⁵Sr und³²P in polykristallinen Sinterkörpern von synthetischem Hydroxylapatit im Temperaturbereich 1000 bis 1400 °C untersucht. Nach sorgfältiger Berücksichtigung von Korngrenzen-Diffusionseffekten ergaben sich für die Diffusion von⁴⁵Ca und⁸⁵Sr gleiche Werte für die Aktivierungsenthalpien und Frequenzfaktoren, und zwar beipH₂O<30 Torr:Q=3,50 ± 0,02 eV;D ₀=41 ± 5 cm²s^–1 und beipH₂O=230 Torr:Q=3,55 ± 0,02 eV;D ₀=20 ± 3 cm²s^–1 Die Abhängigkeit des Kationen-Diffusionskoeffizienten vom Wasserdampfpartialdruck ist vermutlich dadurch bedingt, daß im untersuchten Temperaturbereich feste Lösungen von Hydroxylapatit und Oxyapatit entstehen und Leerstellen im OH^–-Teilgitter den Kationentransport beschleunigen. Der³²P-Transport wurde nur bei 1360 °C undpH₂O < 30 Torr gemessen. Der Diffusionskoeffizient ist um einen Faktor 400 ± 50 kleiner als der entsprechende Diffusionskoeffizient der Kationen.Die Ergebnisse der Diffusionsuntersuchungen werden in Verbindung mit einer einfachen Modellvorstellung zum Retentionsmechanismus der Erdalkalien im Skelett diskutiert.

---

Diffusion of⁴⁵Ca,⁸⁵Sr, and³²P in hydroxyapatite

Summary The transport of⁴⁵Ca,⁸⁵Sr, and³²P in polycrystalline sinter pellets of synthetic hydroxyapatite has been investigated in the temperature range 1000 to 1400 °C. After subtraction of activity transports by grain boundary diffusion processes, equal values of activation enthalpy and frequency factor were found for the lattice diffusion of⁴⁵Ca and⁸⁵Sr: atpH₂O<30 Torr:Q=3,50 ± 0,02 eV,D ₀=41 ± 5 cm²s^–1 and atpH₂O=230 Torr:Q=3,55 ± 0,02 eV,D ₀=20 ± 3 cm²s^–.The dependence of the cation diffusion coefficient on the partial vapour pressure is probably caused by formation of solid solutions of hydroxyapatite and oxyapatite where vacancies of the OH^– sublattice accelerate the cation transport. The diffusion of³²P was investigated only atT=1360 °C andpH₂O<30 Torr. The value obtained is smaller by a factor of 400 ± 50 then the cation diffusion coefficient.The results of the diffusion experiments are discussed in the light of a simple model for the retention mechanism of the alkaline earth metals in the skeleton.

     

Hydrogen bonding interactions in E- or Z-2-phenyl-3-( X'-pyridyl)propenoic acid ( X=2, 3 or 4) assemblies--a molecular modeling study

The agglomeration properties of stereoisomeric 2-phenyl-3-(X-pyridyl)propenoic acids (X=2, 3 or 4) were studied by the PM3 semiempirical quantum chemical method. Calculations revealed that dimers kept together by the intermolecular hydrogen bonding interactions of the carboxylic groups could be built from both stereoisomers irrespective of the position of the nitrogen heteroatom. The dimers of the Z-isomers could also be built through (aromatic)C–H...N hydrogen bonds between the dimer units. The longest agglomerate was the pentamer of the dimers when the nitrogen was in the 2 position. Longer hydrogen-bonded agglomerates than dimers could only be constructed from the E-isomer with the nitrogen in position 4. Here, the trimer of the dimers proved to be the longest hydrogen-bonded entity and similarly to the Z-isomers, the dimer units are kept together by (aromatic)C–H...N intermolecular hydrogen bonds.Figure The helical structure of the pentamer of dimers for the Z-2-phenyl-3-(2-pyridyl)propenoic acid molecule, when in the initial geometry (aromatic)C(4)–H...N close contact was enforced.     

DNAase I hypersensitive sites may be correlated with genomic regions of large structural variation

Helical-twist, roll and torsion-angle variations calculated by the Calladine (1982)-Dickerson (1983) rules were scanned along several nucleotide sequences for which DNAase I cleavage data are available. It has been shown that for short synthetic oligomers DNAase I cuts preferentially at positions of high helical twist (Dickerson & Drew, 1981; Lomonossoff et al., 1981). Our calculations indicate that DNAase I sensitive and hypersensitive sites in chromatin are correlated with regions of successive, large, helical-twist angle variations from regular B-DNA. In many cases these regions exhibit large variations in base-pair roll and backbone torsion angles as well. It has been suggested that DNAase I cuts in the vicinity of cruciforms. However, it was recently demonstrated by Courey & Wang (1983) and Gellert et al. (1983) that such cruciform formation in a negatively supercoiled DNA is kinetically forbidden under physiological conditions. We thus propose that clustering of large twist-angle (and/or roll and backbone torsion angle) variations may be among the conformational features recognized by the enzyme. Specific cuts can then preferentially occur at base-pair steps with high helical twists.