Fluoro-C-glycosides and fluoro-carbasugars, hydrolytically stable and synthetically challenging glycomimetics

International audienceFluoro-C-glycosides and fluoro-carbasugars are a particular subclass of hydrolytically stable glycomimetics that are expected to have different, hopefully improved properties thanks to the stereoelectronic features of the fluoroalkyl moiety. This review summarizes the studies devoted to the synthesis of such structures as well as the studies regarding their conformational behaviour and their potential as carbohydrate analogues

Monitoring of reversible boronic acid–diol interactions by fluorine NMR spectroscopy in aqueous media

International audienceA new convenient method for monitoring boronic acid–diol interactions in aqueous media based on 19 F NMR spectroscopy with fluorinated boronic acid probes is described

Crystal structure of a chiral binaphthyl porphyrin

International audienceCondensation of tetrakis-5,10,15,20-(α,β,α,β-2-aminophenyl)porphyrin atropoisomer with 1,1′-binaphthyl, 2,2′-dimethoxy-3,3′-diacetylchloride afforded the corresponding basket handle porphyrin whose structure has been analyzed by X-ray crystallography. The macrocycle presents a ruffled type plane according to Shelnutt method for classifying and quantifying the out-of-plane and in-plane distortion of a porphyrin. This structure clearly shows the position of the methoxy groups with respect to the center of the porphyrin and their possible role in the enantioselective epoxidation and cyclopropanation of olefins

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

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

Is the 3,4-methylendioxypyrovalerone/mephedrone combination responsible for enhanced stimulant effects? A rat study with investigation of the effect/concentration relationships

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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