An Improved Preparation of Rp and Sp N6, N6, O2′ - Tri-Benzoyl-Adenosine-3′, 5′-Cyclic Phosphoranilidates

Abstract

The conversion of the benzoylated cAMP (2) to the diastereomeric mixture of the anilidates (3) was improved. Replacing the triphenylphosphine/carbon tetrachloride mixture by oxalyl chloride in the presence of a catalytic amount of DMF followed by the addition of aniline not only increased the yield from 27 to 96% but rendered much easier the separation of the diastereoisomers (3), which were formed in approximately equal amounts. This greatly improved the accessability of Rp and Sp-cAMPS (1).     

Cystatin C Is Downregulated in Prostate Cancer and Modulates Invasion of Prostate Cancer Cells via MAPK/Erk and Androgen Receptor Pathways

Cystatin C is believed to prevent tumor progression by inhibiting the activities of a family of lysosomal cysteine proteases. However, little is known about the precise mechanism of cystatin C function in prostate cancer. In the present study, we examined the expression of cystatin C and its association with matrix metalloproteinases 2 (MMP2) and androgen receptor (AR) in a tissue microarray comparing benign and malignant specimens from 448 patients who underwent radical prostatectomy for localized prostate cancer. Cystatin C expression was significantly lower in cancer specimens than in benign tissues (p<0.001) and there was a statistically significant inverse correlation between expression of cystatin C and MMP2 (r_s ² = −0.056, p = 0.05). There was a clear trend that patients with decreased level of cystatin C had lower overall survival. Targeted inhibition of cystatin C using specific siRNA resulted in an increased invasiveness of PC3 cells, whereas induction of cystatin C overexpression greatly reduced invasion rate of PC3 in vitro. The effect of cystatin C on modulating the PC3 cell invasion was provoked by Erk2 inhibitor that specifically inhibited MAPK/Erk2 activity. This suggests that cystatin C may mediate tumor cell invasion by modulating the activity of MAPK/Erk cascades. Consistent with our immunohistochemical findings that patients with low expression of cystatin C and high expression of androgen receptor (AR) tend to have worse overall survival than patients with high expression of cystatin C and high AR expression, induced overexpression of AR in PC3 cells expressing cystatin C siRNA greatly enhanced the invasiveness of PC3 cells. This suggests that there may be a crosstalk between cystatin C and AR-mediated pathways. Our study uncovers a novel role for cystatin C and its associated cellular pathways in prostate cancer invasion and metastasis.     

Surface Plasmon Polaritons Probed with Cold Atoms

Plasmonics - We report on an optical mirror for cold rubidium atoms based on a repulsive dipole potential created by means of a modified recordable digital versatile disc. Using the mirror, we have...     

Inside Cover: Optimized perfusion‐based CUBIC protocol for the efficient whole‐body clearing and imaging of rat organs (J. Biophotonics 5/2018)

Optical tissue clearing is a method allowing post‐mortem deep imaging of organs in three dimensions. By optimizing the CUBIC clearing protocol, the authors provide rapid and simple approach to clear the entire adult rat organism within as little as four days, which is accompanied by the variety of its staining and imaging techniques. The image was captured with polarizers and demonstrates transparent rodent heart with thread‐like crystals of clearing reagent. Further details can be found in the article by Pawe? Matryba et al. ( e201700248 ).

     

Eremophilane derivatives and other constituents from Senecio species

The investigation and reinvestigation respectively of 23 Senecio species afforded 11 further cacalol derivatives, a furoeremophilone, 17 eremophilanes, 4 bisabolene derivatives, a shikimic acid derivative, a bis-prenylated p-hydroxybenzaldehyde, menth-2-en- 1,7-diol and a cumol derivative. The configuration of some eremophilanes have been revised. Structures were elucidated by spectroscopic methods. The results are summarized in a table. The chemotaxonomic aspects agree with those of previous investigations.     

Elevated cholesterol reduces acetylsalicylic acid-mediated platelet acetylation

We describe the role of plasma and platelet cholesterol content in the ability of acetylsalicylic acid (ASA) to acetylate platelet proteins and inhibit platelet function. Platelet susceptibility to ASA was monitored in subjects differing in plasma total cholesterol and in suspensions of cholesterol-enriched or cholesterol-depleted platelets. Platelets from subjects with higher plasma cholesterol (>6 mmol/l) showed reduced platelet sensitivity to ASA (inhibition of platelet aggregation and thromboxane generation by 60% and 68% in 'lower-' vs. 32% and 56% in 'higher-cholesterol' donors; n=13 in each group; p=0.056 and p<0.04, respectively). [Acetyl-1-(14)C] incorporation to platelet proteins in subjects with higher plasma cholesterol was significantly reduced (11.0 vs. 14.6 nmol/g protein, p<0.0001) and correlated significantly with blood total cholesterolemia (R(K)=-0.430, p<0.003) and LDL-cholesterol (R(K)=-0.349, p<0.012), but not with platelet cholesterol content. In conclusion, elevated plasma cholesterol is an important determinant of ASA-induced acetylation of platelets and platelet diminished sensitivity to ASA. The molecular basis of such an association remains obscure, notwithstanding it may constitute a link between sub-optimal platelet response to aspirin and lipid metabolic disorders.     

Broken symmetry between RNA enantiomers in a crystal lattice

Explaining the origin of the homochirality of biological molecules requires a mechanism of disrupting the natural equilibrium between enantiomers and amplifying the initial imbalance to significant levels. Authors of existing models have sought an explanation in the parity-breaking weak nuclear force, in some selectively acting external factor, or in random fluctuations that subsequently became amplified by an autocatalytic process. We have obtained crystals in which l- and d-enantiomers of short RNA duplexes assemble in an asymmetric manner. These enantiomers make different lattice contacts and have different exposures to water and metal ions present in the crystal. Apparently, asymmetry between enantiomers can arise upon their mutual interactions and then propagate via crystallization. Asymmetric racemic compounds are worth considering as possible factors in symmetry breaking and enantioenrichment that took place in the early biosphere.