Aminoacyl-tRNA protein transferases post-translationally conjugate an amino acid from an aminoacyl-tRNA onto the N-terminus of a target polypeptide. The eubacterial aminoacyl-tRNA protein transferase, L/F transferase, utilizes both leucyl-tRNA(Leu) and phenylalanyl-tRNA(Phe) as substrates. X-ray crystal structures with substrate analogues, the minimal substrate phenylalanyl adenosine (rA-Phe) and inhibitor puromycin, have been used to characterize tRNA recognition by L/F transferase. However analyses of these two X-ray crystal structures reveal significant differences in binding. Through structural analyses, mutagenesis, and enzymatic activity assays, we rationalize and demonstrate that the substrate analogues bind to L/F transferase with similar binding affinities using a series of different interactions by the various chemical groups of the analogues. Our data also demonstrates that enlarging the hydrophobic pocket of L/F transferase selectively enhances puromycin inhibition and may aid in the development of improved inhibitors for this class of enzymes.

The attraction of nucleic acids to lipidic compartments is the first step for carriers of potentially inheritable information to self-organise in functionalised synthetic cells. Confocal fluorescence imaging shows that a synthetic amphiphilic peptidyl RNA molecule spontaneously accumulates at the outer bilayer membranes of phospho- and glycolipidic giant vesicles. Cooperatively attractive interactions of -3.4 to -4.0 kcal mol(-1) between a random coil hydrophobic peptide and lipid membranes can thus pilot lipophobic RNA to its compartmentation. The separation of mixed lipid phases in the membranes further enhances the local concentration of anchored RNA.

A short and efficient route to d-lactone-fused cyclopentanoids starting from the easily accessible Diels-Alder adducts between homoallylic alcohol acetates and 1,2,3,4-tetrachloro-5,5-dimethoxycyclopenta-1,3-diene is reported. Since homoallyl alcohols were derived from the corresponding aldehydes RCHO (R = alkyl, aryl) through allyl metal addition, the methodology is broad in scope with regard to the choice of R group. The initially formed 1:1 diastereomeric mixture of adducts were subjected to ruthenium-catalyzed oxidation followed by acid-mediated hydrolysis of the acetate groups to obtain the hemiacetals 6a-e. Alkaline H 2 O 2 -mediated cleavage of the hemiacetals led, after esterification with diazomethane, to a chromatographically separable diastereomeric mixture of 7 and 8 in high overall yield (54-68%).The d-lactone structural motif is extremely important due to its occurrence as core structure in innumerable natural products which often display wide ranging biological activity. 1 The versatility of d-lactones as useful building blocks in the syntheses of natural products 2 as well as unnatural target molecules 3 is well documented. Because of their wide ranging biological activities and their ability to serve as building blocks, the synthesis of d-lactones has garnered a lot of attention, which led to development of various synthetic methods. 4 A cyclopentane ring cis-fused to the d-lactone is a basic subunit of nepetalactone insecticides and such subunits are of interest as synthetic intermediates in organic synthesis. 2,3 During the course of our recent studies on the applications of norbornyl a-diketones, 5 prepared efficiently through a methodology developed in our laboratory, 6 it was observed that an endo-hydroxymethyl group directly furnished the hemiacetals, which were cleaved to give glactones (Scheme 1). 5c Encouraged by the applications of d-lactone-fused cyclopentanoids, 2,3 and the availability of umpteen methods for the synthesis of homoallyl alcohols, 7 we became interested in extending the methodology to the synthesis of the title compounds. To this cause, homoallyl alcohols were identified as suitable precursors, as depicted in the retrosynthetic Scheme 2.The desired homoallylic alcohols could be obtained by well-established allylmetal addition to the corresponding aldehydes RCHO, thus providing a broad range of R groups that may be selected for the purpose. Although the diene 3 has been extensively used in reactions with dienophilic partners, 8 to the best of our knowledge aldehydederived a-substituted homoallyl alcohols were not fully explored as dieneophiles. Our initial experiments on Diels-Alder reaction of 1,2,3,4-tetrachloro-5,5-dimethoxycyclopenta-1,3-diene (3) and homoallyl alcohols led to complications. To circumvent this problem, we decided to protect the alcohol group of the homoallyl alcohols as acetates before subjecting them to the Diels-Alder reaction. The required dienophiles 2a-e were prepared by zincmediated allylation of aldehydes 1a-e followed by acetyl protection...

We are reporting on the utility of commercial vinyl isocyanate for a practical synthetic route from adenosine to N(6)-bis-demethylpuromycin in seven steps and 65% overall yield. A clean one-pot conversion of 3'-bromo-2'-carbamoyl derivative 8 to 3'-amino-3'-deoxyadenosine derivative 10 is the main feature of this synthetic pathway. This synthesis is the shortest synthetic route toward 3'-(aminoacylamido)deoxyadenosines to date.