15 research outputs found
Bibliothèques et bibliothécaires d\u27outre-mer
Cette journée, qui s\u27est tenue dans les locaux de l’enssib, le mardi 13 septembre 2011, de 9h30 à 17h30, visait à dresser un état des lieux des défis auxquels les bibliothèques universitaires d’outre-mer sont confrontées. Aussi la journée a été organisée plus particulièrement autour de trois séquences : l’une, générale, destinée à présenter ces bibliothèques ; les deux autres, thématiques, destinées à aborder deux sujets qui semblent particulièrement importants dans ce contexte : la question de la formation des personnels et celle des politiques de coopération
Biomolecular simulations: From dynamics and mechanisms to computational assays of biological activity
Biomolecular simulation is increasingly central to understanding and designing biological molecules and their interactions. Detailed, physics‐based simulation methods are demonstrating rapidly growing impact in areas as diverse as biocatalysis, drug delivery, biomaterials, biotechnology, and drug design. Simulations offer the potential of uniquely detailed, atomic‐level insight into mechanisms, dynamics, and processes, as well as increasingly accurate predictions of molecular properties. Simulations can now be used as computational assays of biological activity, for example, in predictions of drug resistance. Methodological and algorithmic developments, combined with advances in computational hardware, are transforming the scope and range of calculations. Different types of methods are required for different types of problem. Accurate methods and extensive simulations promise quantitative comparison with experiments across biochemistry. Atomistic simulations can now access experimentally relevant timescales for large systems, leading to a fertile interplay of experiment and theory and offering unprecedented opportunities for validating and developing models. Coarse‐grained methods allow studies on larger length‐ and timescales, and theoretical developments are bringing electronic structure calculations into new regimes. Multiscale methods are another key focus for development, combining different levels of theory to increase accuracy, aiming to connect chemical and molecular changes to macroscopic observables. In this review, we outline biomolecular simulation methods and highlight examples of its application to investigate questions in biology.
This article is categorized under:
Molecular and Statistical Mechanics > Molecular Dynamics and Monte‐Carlo Methods
Structure and Mechanism > Computational Biochemistry and Biophysics
Molecular and Statistical Mechanics > Free Energy Method
Coopération de la médiathèque du Port
Intervention de Michel Etheve, directeur de la médiathèque du Port, La Réunion
Formation et recrutement des bibliothécaires en Outre-mer : symptômes des relations entre pouvoir central et collectivités d\u27outre-mer ?
Table ronde sur la formation et le recrutement des bibliothécaires en Outre-mer animée par Michel Etheve (directeur de la médiathèque du Port, La Réunion), Laurent Tesoka (directeur de l\u27IDOM) et Christophe Catanèse (responsable de la formation des élèves conservateurs, enssib)
Stable Analogues of Aminoacyl-tRNA for Inhibition of an Essential Step of Bacterial Cell-Wall Synthesis [ J. Am. Chem. Soc
Synthesis of carbapenems containing peptidoglycanmimetics and inhibition of the cross-linking activity of a transpeptidase of the L,D specificity
International audienceThe carbapenem class of β‐lactams has been optimized against Gram‐negative bacteria producing extended‐spectrum β‐lactamases by introducing substituents at position C2. Carbapenems are currently investigated for the treatment of tuberculosis as these drugs are potent covalent inhibitors of l,d‐transpeptidases involved in mycobacterial cell wall assembly. The optimization of carbapenems for inactivation of these unusual targets is sought herein by exploiting the nucleophilicity of the C8 hydroxyl group to introduce chemical diversity. As β‐lactams are structure analogs of peptidoglycan precursors, the substituents were chosen to increase similarity between the drug and the substrate. Fourteen peptido‐carbapenems were efficiently synthesized. They were more effective than the reference drug, meropenem, owing to the positive impact of a phenethylthio substituent introduced at position C2 but the peptidomimetics added at position C8 did not further improve the activity. Thus, position C8 can be modified to modulate the pharmacokinetic properties of highly efficient carbapenems
Inventory, evolution and expression profiling diversity of the LEA (late embryogenesis abundant) protein gene family in Arabidopsis thaliana
International audienc
Synthesis of tRNA analogues containing a terminal ribose locked in the South conformation to study tRNA-dependent enzymes
International audienceSynthesis and biological evaluation of tRNA analogues containing a terminal ribose locked in the South conformation
Phosphine-Mediated Bioconjugation of the 3′-End of RNA
International audienceStaudinger ligation is an attractive bio-orthogonal reaction that has been widely used to tag proteins, carbohydrates, and nucleic acids. Here, we explore the traceless variant of the Staudinger ligation for 3′-end modification of oligoribonucleotides. An azido-containing dinucleotide was used to study the ligation. Nine phosphines containing reactive groups, affinity purification tags, or photoswitch probes have been successfully obtained. The corresponding modified dinucleotides were synthesized and characterized by LC/MS. Mechanistic interpretations of the reaction are proposed, in particular, the unprecedented formation of an oxazaphospholane nucleotide derivative, which was favored by the vicinal position of 2′-N3 and 3′-OH functional groups on the terminal ribose has been observed. The post-functionalization of a 24-nt RNA with a photoactivable tag is also reported
Click and release chemistry for activity‐based purification of β‐lactam targets
International audienceβ-Lactams, the cornerstone of antibiotherapy, inhibit multiple and partially redundant targets referred to as transpeptidases or penicillin-binding proteins. These enzymes catalyze the essential cross-linking step of the polymerization of cell wall peptidoglycan. The understanding of the mechanisms of action of β-lactams and of resistance to these drugs requires the development of reliable methods to characterize their targets. Here, we describe an activity-based purification method of β-lactam targets based on click and release chemistry. We synthesized alkyne-carbapenems with suitable properties with respect to the kinetics of acylation of a model target, the Ldtfm L,D-transpeptidase, the stability of the resulting acylenzyme, and the reactivity of the alkyne for the cycloaddition of an azido probe containing a biotin moiety for affinity purification and a bioorthogonal cleavable linker. The probe provided access to the fluorescent target in a single click and release step