G. Precigoux

Parallel and antiparallel (G.GC)2 triple helix fragments in a crystal structure

Nucleic acid triplexes are formed by sequence-specific interactions between single-stranded polynucleotides and the double helix. These triplexes are implicated in genetic recombination in vivo and have application to areas that include genome analysis and antigene therapy. Despite the importance of the triple helix, only limited high-resolution structural information is available. The x-ray crystal structure of the oligonucleotide d(GGCCAATTGG) is described; it was designed to contain the d(G˙GC)2 fragment and thus provide the basic repeat unit of a DNA triple helix. Parameters derived from this crystal structure have made it possible to construct models of both parallel and antiparallel triple helices.

Comparison of the structures of the cubic and tetragonal forms of horse-spleen apoferritin.

Horse-spleen apoferritin is known to crystallize in three different space groups, cubic F432, tetragonal P42(1)2 and orthorhombic P2(1)2(1)2. A structure comparison of the cubic and tetragonal forms is presented here. Both crystal forms were obtained by the vapor-diffusion technique and data were collected at 2.26 A (cubic crystal) and 2.60 A (tetragonal crystal) resolution. Two main differences were observed between these crystal structures: (i) whereas intermolecular contacts only involve salt-bridge type interactions via cadmium ions in the cubic structure, two types of interactions are observed in the tetragonal crystal (cadmium-ion-mediated salt bridges and hydrogen-bonding interactions) and (ii) cadmium ions bound in the threefold axes of ferritin molecules exhibit lower site-occupation factors in the tetragonal structure than in the cubic one.

Immunoreactive gonadotropin-releasing hormone-like material in the brain and the pituitary gland during the periovulatory period in the brown trout (Salmo trutta L.): Relationships with the plasma and pituitary gonadotropin

In fish there are few data on the gonadotropin-releasing hormone (Gn-RH) neurosecretory activity, which could explain long- and short-term variations of the gonadotropin secretion. There is no biological species specificity between mammal and fish Gn-RH; although there is a structural difference, they are, on the contrary, characterized by a high immunological specificity which does not allow measurement of fish Gn-RH using radioimmunoassay for LH-RH. We have synthesized salmon Gn-RH according to the formula recently proposed by Sherwood (N. Sherwood, L. Eiden, M. Brownstein, J. Spies, J. Rivier, and W. Vale, 1983. Proc. Natl. Acad. Sci. USA 80, 2794-2798). Its activity has been tested by its ability to stimulate the gonadotropin hormone (GtH) secretion in vivo in testosterone-implanted juvenile rainbow trout, and for the recognition of synthesized Gn-RH (s-Gn-RH) perykaria by a specific antibody raised against the s-Gn-RH in regions of the brain described as containing LH-RH immunoreactive-like material. A radioimmunoassay has been developed for the salmon Gn-RH, and its specificity to measure trout Gn-RH has been tested. Using this assay, the brain and pituitary Gn-RH contents have been measured throughout the final phases of maturation and ovulation. Brain Gn-RH increases from the end of vitellogenesis (8.9 +/- 0.76 ng/brain) to ovulation (more than 15 ng/brain). Pituitary Gn-RH is lower (1.58 +/- 0.69 ng/pituitary) at the end of vitellogenesis and follows a similar profile as in the brain, except for a significant decrease just prior the beginning of oocyte maturation. The correlations between Gn-RH levels and GtH pituitary and plasma levels show that total brain Gn-RH is never correlated to the GtH, suggesting that the increase in the brain Gn-RH content is related to a Gn-RH system closely related to maturation and ovulation, which remains to be investigated. On the contrary, pituitary Gn-RH levels are well correlated with pituitary and plasma GtH levels, indicating that pituitary Gn-RH levels might represent a good index of the Gn-RH neurosecretory activity in the fish hypothalamohypophysial complex, given the absence of a portal system in teleost.

X-ray structure of recombinant horse L-chain apoferritin at 2.0 angstrom resolution: Implications for stability and function

Abstract The X-ray structure of recombinant horse L-chain (rL) apoferritin, solved at 2.0 Å resolution with a final R factor of 17.9%, gives evidence that the residue at position 93 in the sequence is a proline and not a leucine, as found in earlier sequencing studies. The structure is isomorphous with other apoferritin structures, and we thus draw particular attention to those structural features which can be related to the stability and function of the protein. Analysis of hydrogen bonding and salt bridge interactions shows that dimers and tetramers are the most stable molecular entities within the protein shell: a result confirming earlier biophysical experiments. The stability of horse rL apoferritin to both dissociation into subunits at acidic pH values and to complete unfolding in guanidine chloride solutions is compared with that of other apoferritins. This emphasizes the role played by the salt bridge in the stability of this protein family. The horse rL apoferritin is significantly more resistant to denaturation than horse spleen ferritin, which in turn is more resistant than any human rH apoferritins, even those for which a salt bridge is restored. Finally, this structure determination not only establishes that a preformed pocket exists in L-chain apoferritin, at a site known to be able to bind porphyrin, but also underlines the particular function of a cluster of glutamic acids (E53, E56, E57 and E60) located at the entrance of this porphyrin-binding pocket.

Chimie organometallique ☆: XXII. Synthese d'arenes substitues par addition d'un nucleophile a un arene chrome tricarbonyle puis par decomplexation oxydante du metal

Abstract The product distribution obtained in addition reactions of −CH(CH3)CN to an arenechromium tricarbonyl is studied. The major product obtained after oxidative removal of the metal corresponds to nucleophilic addition on an arene carbon atom which is in an eclipsed position with respect to the carbonyl group of the Cr(CO)3 unit of the most stable conformer. The synthesis of the corresponding acid represents an example of arenechromium tricarbonyl chemistry applied to synthesis of an organic compound having pharmaceutical properties and which by classical methods could only be synthesized via a multi step process.

Structure of a Monoclinic Crystal Form of Cytochrome b1 (Bacterioferritin) from E. coli

Crystals of E. coli cytochrome b1, alias bacterioferritin, were grown fr om a low ionic strength solution. The resulting monoclniic P21 structure was solved by molecular replacement and refined using noncrystallographi c symmetries applied to the fundamental unit, consisting of two protein subunits and a single haem. From the Patterson self-rotation results it was shown that the asymmetric unit of the monoclinic crystal consists of 12 such dimers and corresponds to a complete, nearly spherical, molecule of bacterioferritin (M4 = 450 kDa) of 432 point-group symmetry. It is thus the most symmetrical cytochrome. As previously determined for the tetragonal form, the haem is located in a special position on a local twofold axis of the dimer. A bimetal centre is also observed within the four-helix bundle of each monomer; a metal-binding site is located on the fourfold axis.

Bioactive and model peptides characterized by the helicogenic (αMe)Phe residue

Abstract We have synthesized and fully characterized the hypersweet super-aspartame analogue p CN-C6H4-NHCO-L-Asp-L-(αMe)Phe-OME 1; the [D-(αMe)Phe]3-analogue of the formyl-methionyl tripeptide chemoattractant HCO-L-Met-L-Leu--D-(αMe)Phe-OMe 2, the first D-chemotactic peptide being found more active than its L-diastereomer; and the model pentapeptide p BrBz-D-(αMe)Phe-(Aib)2-D-(αMe)Phe-Aib-O t Bu 3. The preferred conformation of the three peptides, as determined by X-ray diffraction analyses, is discussed in terms of the proposed receptor models for sweet perception [peptide 1] and neutrophil chemotaxis [peptide 2], and as a promising candidate for molecular recognition studies [peptide 3].

Structure radiocristallographique du veratrole-chrome-tricarbonyle; etudes RMN 1H d'arene-chrome-tricarbonyles ortho-disubstitues et regioselectivite de l'addition α-cyanocarbanion

Abstract The structure of veratroletricarbonylchromium in the solid state has been determined by X-ray study. The projection of the chromium atom on the arene plane is displaced by 0.06(1) A from the center of symmetry of the benzene ring toward the side opposite to the methoxy groups, and the conformation of the tripod is almost staggered with regard to the aromatic ring. Comparison between the 1 H NMR spectra of veratrole and veratroletricarbonylchromium shows that the protons ortho to the methoxy groups are less shielded during the complexation of veratrole with the Cr(CO) 3 entity and their chemical shift occurs at lower field. From these observations, it is deduced that there is a relationship between the chemical shifts of these protons and the regioselectivity of the addition to the aromatic ring of an α-cyanocarbanion. The same conclusion is extended to the case of other disubstituted arenetricarbonylchromium complexes.

Chimie organometallique: XXX. Etude par resonance magnetique nucleaire du proton et par radiocristallographie du N-methylindolechrome-tricarbonyle

Abstract The structure of N -methylindolechromium tricarbonyl ( 4 ) in the solid state has been determined by X-ray crystallography. The projection of the chromium atom on the N -methylindole plane does not coincide with the center of symmetry of the benzene ring; the tripod is distorted and the overall conformation of the complex is gauche rather than eclipsed. Study of the 1 H NMR spectrum of complex 4 in solution at +20°C and −38°C leads to similar conclusions. The results explain the nucleophilic attack at carbon atoms 4 and 7 of complex 4 .

Some hypothesese about interactions between estrogen and androgen and their possible receptors

Abstract A 17β hydroxy function on the D ring is a common part of natural steriods which have estrogenic or androgenic activity. Crystal structures of such steroids show that there are two possible directions for hydrogen bonds to the 17β hydroxy function whatever the activity of the molecule. If similar interactions occur on binding to the biological ‘receptors’ it is proposed that the specificity of activity (estrogen or androgen) might result from the particular geometry of the A ring area of the steroids relative to this part of the molecule.