Efficient Access to Peptidyl‐RNA Conjugates for Picomolar Inhibition of Non‐ribosomal FemXWv Aminoacyl Transferase

Peptidyl–RNA conjugates have various applications in studying the ribosome and enzymes participating in tRNA‐dependent pathways such as Fem transferases in peptidoglycan synthesis. Herein a convergent synthesis of peptidyl–RNAs based on Huisgen–Sharpless cycloaddition for the final ligation step is developed. Azides and alkynes are introduced into tRNA and UDP‐MurNAc‐pentapeptide, respectively. Synthesis of 2′‐azido RNA helix starts from 2′‐azido‐2′‐deoxyadenosine that is coupled to deoxycytidine by phosphoramidite chemistry. The resulting dinucleotide is deprotected and ligated to a 22‐nt RNA helix mimicking the acceptor arm of Ala‐tRNA^Ala by T4 RNA ligase. For alkyne UDP‐MurNAc‐pentapeptide, meso‐cystine is enzymatically incorporated into the peptidoglycan precursor and reduced, and L ‐Cys is converted to dehydroalanine with O‐(mesitylenesulfonyl)hydroxylamine. Reaction of but‐3‐yne‐1‐thiol with dehydroalanine affords the alkyne‐containing UDP‐MurNAc‐pentapeptide. The Cu^I‐catalyzed azide alkyne cycloaddition reaction in the presence of tris[(1‐hydroxypropyl‐1H‐1,2,3‐triazol‐4‐yl)methyl]amine provided the peptidyl‐RNA conjugate, which was tested as an inhibitor of non‐ribosomal FemX_Wv aminoacyl transferase. The bi‐substrate analogue was found to inhibit FemX_Wv with an IC₅₀ of (89±9) pM , as both moieties of the peptidyl–RNA conjugate contribute to high‐affinity binding.     

gem‐Difluorocarbadisaccharides: Restoring the exo‐Anomeric Effect

Molecular mimicry is an essential part of the development of drugs and molecular probes. In the chemical glycobiology field, although many glycomimetics have been developed in the past years, it has been considered that many failures in their use are related to the lack of the anomeric effects in these analogues. Additionally, the origin of the anomeric effects is still the subject of virulent scientific debates. Herein, by combining chemical synthesis, NMR methods, and theoretical calculations, we show that it is possible to restore the anomeric effect for an acetal when replacing one of the oxygen atoms by a CF₂ group. This result provides key findings in chemical sciences. On the one hand, it strongly suggests the key relevance of the stereoelectronic component of the anomeric effect. On the other hand, the CF₂ analogue adopts the natural glycoside conformation, which might provide new avenues for sugar‐based drug design.     

Broadcasting, Scalability, and Reconfigurability Aspects in an All-Optical Network Architecture

All-optical networks are a sound answer to the huge data traffic demand expected for the forthcoming information society. Interesting networking aspects are the broadcasting, scalability, and reconfiguration in an all-optical environment. These issues are addressed in the present article for an all-optical network called MATRIX, which is time slotted and uses packet switching. The architecture enables the all-optical interconnection of a large number of nodes with both a small number of wavelengths and wavelength continuity based on a consequent exploitation of wavelength-division multiplexing and space-division multiplexing (i.e., multiple fibers per cable are used). For an efficient use of the resources, each node is equipped with multiple transmitters and receivers, respectively. Two different broadcasting schemes are investigated. An analytical model is developed, and the corresponding simulation results are in good agreement. It is further shown how different networks of arbitrary size can be interconnected to larger all-optical network clusters, thereby providing scalability not only with respect to the number of nodes but also to the geographical extension. Finally, wavelength reassignments allow change of optical paths through the network in case of changing traffic patterns or network failures in order to best exploit the available network resources. The total number of possible configurations is determined by the theory of Latin Squares.     

On the occasion of being awarded the title of doctor honoris causa at the university of montpellier II

Abstract

Je suis très honoréde recevoir le titre de Docteur Honoris Causa de 1 Université de Montpellier, une des Universités les plus anciennes et les plus prestigieuses de France et d'Europe. Je considère que c′est une preuve de genérosité de la part des autorités de I'Université que d'honorer quelqu'un qui a une lacune manifeste. En efet, si je parle, je préfére I'anglais. Si je pense, je le fais naturellement en allemand. Et sije me tais, c'est souvent en français. J'espére que le grand honneur que l'on me fait ne va donc pas à l'encontre de la constitution française.

Vous savez, aujourd'hui, il est trés facile de communiquer par Fax et e-mail. Mais, sans une langue commune, aucune communication n'est possible. Heureusement, les scientifiques ont inventé des langues formelles et logiques comme le FORTRAN et le C++. Mais ces langues ne suflsent pas pour exprimer la gratitude que J'éprouve à être ici, dans une robe magnijique et unique. Je suis persuadé que j'ai fini par éveiller l'admiration de ma chère epouse et peut-être aussi le respect de quelques personnes présentes dans cette vénérable salle. Mais pour exprimer quelques pensées plus sérieuses, “Lmore earnest”, il me faut changer ma langue muette contre ma langue parlante, l'anglais.     

Longitudinal investigation of the metabolome of 3D aggregating brain cell cultures at different maturation stages by 1H HR-MAS NMR

Analytical and Bioanalytical Chemistry - The aim of the present study was to establish the developmental profile of metabolic changes of 3D aggregating brain cell cultures by 1H high-resolution...