Both systemic and local application of Granulocyte-colony stimulating factor (G-CSF) is neuroprotective after retinal ganglion cell axotomy

Background  

The hematopoietic Granulocyte-Colony Stimulating Factor (G-CSF) plays a crucial role in controlling the number of neutrophil progenitor cells. Its function is mediated via the G-CSF receptor, which was recently found to be expressed also in the central nervous system. In addition, G-CSF provided neuroprotection in models of neuronal cell death. Here we used the retinal ganglion cell (RGC) axotomy model to compare effects of local and systemic application of neuroprotective molecules.     

Diastereoselective synthesis of 2,3,5-trisubstituted tetrahydrofurans via cyclofunctionalization reactions. Evidence of stereoelectronic effects.

The work described herein considers the impact of stereoelectronic effects and allylic 1,3-strain in controlling the cyclofunctionalization reaction when a hydroxyl group is at the allylic position. The stereoelectronic arguments are supported by independent iodocyclization reactions performed using two secondary alcohols. The transition-state pathways involved in these reactions are established through a comparison of relative reaction rates. A bi-directional approach is used to demonstrate the potential of the iodocyclization reaction to differentiate a terminus in molecules with a pseudo C(2) axis of symmetry, showing that two-directional synthesis can be used to differentiate between alternative transition-state pathways.     

The synthesis of 2′–5′ linked oligoribonucleotides

The use of alkylsilyl protecting groups provides a rapid route to 3′,5′-diprotected ribonucleosides which are easily coupled via the phosphorodichloridite procedure to produce 2′–5′ linked ribonucleotides.     

Opening of tartrate acetals using dialkylboron bromide: evidence for stereoselectivity downstream from ring fission

Johnson-type acetals derived from dimethyl tartrate give, after opening with Me(2)BBr and cuprate displacement, secondary alcohols with high diastereoselectivity (>30:1). The mechanism proposed for the induction of diastereoselectivity is downstream from the ring fission. It implies a direct participation of the Lewis acid as a source of nucleophile and the stereospecific transformation of the resulting bromo acetal through an invertive and temperature-dependent process. The acetals are prepared by reaction of the desired aldehyde with dimethyl tartrate. Removal of the auxiliary is accomplished through SmI(2) reduction or by an addition-elimination protocol using methoxide.     

Nonaqueous oxidation of phosphites to phosphates in nucleotide synthesis

$\text{m}$-Chloroperbenzoic acid in methylene chloride represents a rapid non-aqueous method for the conversion of phosphites to phosphates during oligonucleotide synthesis both in solution and on a solid support.     

Analysis of Pure Rotational and Vibration‐rotational Spectra of NaCl X 1Σ+ and Quantum‐chemical Calculation of Related Molecular Properties

We fitted published frequency and wave number data for pure rotational and vibration‐rotational spectra, respectively, of ²³Na³⁵Cl and ²³Na³⁷Cl to derive parameters related to potential energy and to the rotational g factor. For comparison with these experimental data we undertook quantum‐chemical computation of adiabatic corrections, rotational and vibrational g factors, electric dipolar moment and its derivative as a function of internuclear distance in a range near R_e as a test of an algebraic approach to spectral analysis; experimental, 0.0287 ± 0.0014, and calculated, 0.02149, values of g_r at R_e are in moderate agreement. The combined results are discussed from a point of view of computational spectrometry.     

Mass spectrometry of trialkylsilyl and acyl derivatives of 2′-deoxynucleosides

The electron impact mass spectra of monosilyl and mixed acyl-silyl derivatives of 2′-deoxynucleosides are described in detail. (Silyl = tert-butyldimethylsilyl, cyclo-tetramethylene-isopropylsilyl, or cyclo-tetramethylene-tert-butylsilyl; acyl = acetyl or trifluoroacetyl.) The interpretation of the fragmentation pathways was aided by metastable ion decomposition studies, precise mass and deuterium labelling measurements. Mass spectrally, the acyl substituents are mostly ‘passive’ and have (with possibly one exception) little fragmentation directing capability. In contrast, the silyl groups have powerful fragmentation directing properties. Elimination of the bulky alkyl radical R^˙ (tert-butyl or isopropyl) from the molecular ion produces the siliconium ion, [M–R]⁺, which is the precursor for most of the other prominent ions in the spectra. These arise from ‘siliconium ion rearrangements’ resulting from the interaction of the positively charged siliconium ion centre with the electron dense regions (i.e. oxygens) in the molecule, to form cyclic silyloxonium ions which subsequently decompose. Since the interacting oxygen and silicon must be sterically accessible, the fragment ion types and their abundances are very dependent upon structure. Consequently, [M–R]⁺ ions formed from 3′- or 5′-O-silyl groups give rise to different sets of daughter ions which, for the most part, are not found, or have very low abundances, in the mass spectra of underivatized or trimethylsilylated nucleosides. Detailed information on sugar and base moieties and isomeric substitution is readily obtained.     

Evolved CYP102A1 (P450BM3) variants oxidise a range of non-natural substrates and offer new selectivity options

The evolution of CYP102A1 variants with enhanced activity and altered specificity characteristics.