Structure of an RNA helix with pyrimidine mismatches and cross-strand stacking

The structure of a 22-base-pair RNA helix with mismatched pyrimidine base pairs is reported. The helix contains two symmetry-related CUG sequences: a triplet-repeat motif implicated in myotonic dystrophy type 1. The CUG repeat contains a U–U mismatch sandwiched between Watson–Crick pairs. Additionally, the center of the helix contains a dimerized UUCG motif with tandem pyrimidine (U–C/C–U) mismatches flanked by U–G wobble pairs. This region of the structure is significantly different from previously observed structures that share the same sequence and neighboring base pairs. The tandem pyrimidine mismatches are unusual and display sheared, cross-strand stacking geometries that locally constrict the helical width, a type of stacking previously associated with purines in internal loops. Thus, pyrimidine-rich regions of RNA have a high degree of structural diversity.

Design, Synthesis of New Pyridine and Pyrimidine Sugar Compounds as Antagonists Targeting the ERα via Structure-Based Virtual Screening

Background: New aryl substituted cyclohepta[b]pyridine and cyclohepta[d]pyrimidine derivatives were synthesized. The sugar hydrazones of the synthesized pyridine and pyrimidine compounds were also prepared. </P><P> Method: In addition, the 1,3,4-oxadiazolyl acyclic C-nucleoside analogs of the pyridine system were prepared. The hemolytic, prebiotic, anticancer and antimicrobial activities of some of the synthesized compounds were also studied. Compounds 10 and 12 showed high activity against MCF-7, HEPG-2 and HCT-116 cell lines with IC50 at range 3.56-8.55 &#181;g/mL. In addition, the synthesized condensed thiopyrimidine derivative 10 exhibited more potent bactericidal activity while compound 7 demonstrated potent antifungal activity against Aspergillus niger. Furthermore, the synthetic compounds of the pyrimidine base promoted the growth of lactic acid bacteria. </P><P> Results: The predicted binding patterns of three of the prepared derivatives as possible antagonists against ERα were investigated which showed good binding patterns.

Enantioselective Bioreduction of Prochiral Pyrimidine Base Derivatives by Boni Protect Fungicide Containing Live Cells of Aureobasidium pullulans

The enzymatic enantioselective bioreduction of prochiral 1-substituted-5-methyl-3-(2-oxo-2-phenylethyl)pyrimidine-2,4(1H,3H)-diones to corresponding chiral alcohols by Boni Protect fungicide containing live cells of Aureobasidium pullulans was studied. The microbe-catalyzed reduction of bulky-bulky ketones provides enantiomerically pure products (96–99% ee). In the presence of A. pullulans (Aureobasidium pullulans), one of the enantiotopic hydrides of the dihydropyridine ring coenzyme is selectively transferred to the si sides of the prochiral carbonyl group to give secondary alcohols with R configuration. The reactions were performed under various conditions in order to optimize the procedure with respect to time, solvent, and temperature. The present methodology demonstrates an alternative green way for the synthesis of chiral alcohols in a simple, economical, and eco-friendly biotransformation.

Abiotic synthesis of purine and pyrimidine ribonucleosides in aqueous microdroplets

Aqueous microdroplets (<1.3 µm in diameter on average) containing 15 mM d-ribose, 15 mM phosphoric acid, and 5 mM of a nucleobase (uracil, adenine, cytosine, or hypoxanthine) are electrosprayed from a capillary at +5 kV into a mass spectrometer at room temperature and 1 atm pressure with 3 mM divalent magnesium ion (Mg2+) as a catalyst. Mass spectra show the formation of ribonucleosides that comprise a four-letter alphabet of RNA with a yield of 2.5% of uridine (U), 2.5% of adenosine (A), 0.7% of cytidine (C), and 1.7% of inosine (I) during the flight time of ∼50 µs. In the case of uridine, no catalyst is required. An aqueous solution containing guanine cannot be generated under the same conditions given the extreme insolubility of guanine in water. However, inosine can base pair with cytidine and thus substitute for guanosine. Thus, a full set of ribonucleosides to generate the purine–pyrimidine base pairs A-U and I-C are spontaneously generated in aqueous microdroplets under similar mild conditions.