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.     

Synthesis of orthogonally protected vicinal diamines with amino acid-based skeleton

A convenient route to amino acid-based orthogonally protected 1,2-diamines starting from materials readily available for a peptide chemist is presented. The key step of the procedure is the Mitsunobu reaction of N-protected aminoalcohol, obtained by the reduction of commercially available Z- or Boc-protected amino acid, with imidodicarbonate or sulfonylcarbamate related to standard amino-protecting groups used in peptide chemistry yielding triprotected vicinal diamines.     

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.     

Mapping the substrate binding site of phenylacetone monooxygenase from Thermobifida fusca by mutational analysis

Baeyer-Villiger monooxygenases catalyze oxidations that are of interest for biocatalytic applications. Among these enzymes, phenylacetone monooxygenase (PAMO) from Thermobifida fusca is the only protein showing remarkable stability. While related enzymes often present a broad substrate scope, PAMO accepts only a limited number of substrates. Due to the absence of a substrate in the elucidated crystal structure of PAMO, the substrate binding site of this protein has not yet been defined. In this study, a structural model of cyclopentanone monooxygenase, which acts on a broad range of compounds, has been prepared and compared with the structure of PAMO. This revealed 15 amino acid positions in the active site of PAMO that may account for its relatively narrow substrate specificity. We designed and analyzed 30 single and multiple mutants in order to verify the role of these positions. Extensive substrate screening revealed several mutants that displayed increased activity and altered regio- or enantioselectivity in Baeyer-Villiger reactions and sulfoxidations. Further substrate profiling resulted in the identification of mutants with improved catalytic properties toward synthetically attractive compounds. Moreover, the thermostability of the mutants was not compromised in comparison to that of the wild-type enzyme. Our data demonstrate that the positions identified within the active site of PAMO, namely, V54, I67, Q152, and A435, contribute to the substrate specificity of this enzyme. These findings will aid in more dedicated and effective redesign of PAMO and related monooxygenases toward an expanded substrate scope.     

Induction of apoptosis and necrosis in lymphocytes by the cis-Pt(II) complex of 3-aminoflavone in comparison with cis-DDP

cis-Diamminedichloroplatinum(II) (cis-DDP) is one of the most widely administrated antitumor drugs. However, the use of cis-DDP is severely limited because of its toxic side effects. Therefore, efforts are concentrated on the development of improved platinum compounds with a broader activity spectrum and effectiveness in chemotherapy, but lower toxicity. Beneficial properties of flavonoids, e.g. their antitumor activity, encouraged scientists to synthesize cis-bis(3-aminoflavone)dichloroplatinum(II). Abilities of these compounds to induce apoptosis and necrosis were compared by use of trypan blue, fluorochrome staining (Hoechst 33258/propidium iodide double staining) and TUNEL assays. The cytotoxicity was evaluated by MTT. The results obtained show that the cis-Pt(II) complex of 3-aminoflavone is less toxic than cis-DDP. However, the former compound has a faster rate of apoptosis induction in lymphocytes than the latter. The cis-Pt(II) complex of 3-aminoflavone induces apoptosis in normal lymphocytes to a lesser degree and could be a potential antitumor drug.     

Demodex microti n. sp. (Acari: Demodecidae) in Microtus arvalis (Pallas) (Rodentia, Cricetidae) with a checklist of the demodecid mites of cricetids

Demodex microti n. sp. (Acari, Demodecidae) is described from the skin of the genital area of the common vole Microtus arvalis (Pallas) in Poland based on the morphology of the adult and immature stages. The new species appears most similar to D. cricetuli Hurley & Desch, 1994 from the gray dwarf hamster, Cricetulus migratorius (Pallas), but differs in the following features: the supracoxal spines are conical and located at the edge of the gnathosoma, the spines of the terminal segment of palp are three, single-tined, the opisthosomal organ is narrow and elongated in males and bubble-shaped in females, the vulva is located below the incision of the fourth pair of epimeral plates, eggs are oval. The differences also relate to body size and proportions, D. microti n. sp. being smaller and slender. The new species occurred in all of the rodents examined. A checklist of demodecid mites in cricetids world-wide is also provided.     

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).