65 research outputs found
Capsules hélicoïdales auto-organisées par repliement d'oligoamides aromatiques pour la reconnaissance moléculaire
La reconnaissance molĂ©culaire constitue l une des questions fondamentales les plus discutĂ©es dans le domaine de la chimie supramolĂ©culaire. Cette thĂšse prĂ©sente la conception, la synthĂšse et l Ă©tude des propriĂ©tĂ©s de capsules hĂ©licoĂŻdales auto-organisĂ©es par repliement d oligoamides aromatiques. Ces rĂ©cepteurs sont constituĂ©s d une chaĂźne oligomĂ©rique se repliant en hĂ©lice et comprenant une sĂ©quence d unitĂ©s codant pour des diamĂštres diffĂ©rents. Le repliement de l oligomĂšre donne naissance Ă une cavitĂ© pouvant accueillir des molĂ©cules invitĂ©es. La grande modularitĂ© des sĂ©quences, permettant une Ă©volution contrĂŽlĂ©e des structures des foldamĂšres, donne lieu Ă la reconnaissance sĂ©lective et anticipĂ©e de substrats d intĂ©rĂȘts biologiques. Le phĂ©nomĂšne d encapsulation a Ă©tĂ© mis en Ă©vidence en solution par spectroscopie RMN et CD, et dans le solide par diffraction des rayons X.Molecular recognition is one of the major challenges of supramolecular chemistry. Here, we present the design, synthesis and study of helical capsules properties self-organised by aromatic oligoamide folding. These receptors consist of oligomeric chains that fold into a helical conformation and comprise of a sequence of units which code for different diameters. Oligomeric folding defines a cavity which can recognize guests. The great modularity of the sequences has allowed a controlled evolution of foldamer structure resulting in the selective and predict recognition of biological substrates. The phenomenon of encapsulation was demonstrated in solution by NMR and CD spectroscopy and in the solid state by X-ray diffraction.BORDEAUX1-Bib.electronique (335229901) / SudocSudocFranceF
Detection of decreased glomerular filtration rate in intensive care units: serum cystatin C versus serum creatinine
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Capsules hĂ©licoĂŻdales auto-organisĂ©es par repliement dâoligoamides aromatiques pour la reconnaissance molĂ©culaire
Molecular recognition is one of the major challenges of supramolecular chemistry. Here, we present the design, synthesis and study of helical capsules properties self-organised by aromatic oligoamide folding. These receptors consist of oligomeric chains that fold into a helical conformation and comprise of a sequence of units which code for different diameters. Oligomeric folding defines a cavity which can recognize guests. The great modularity of the sequences has allowed a controlled evolution of foldamer structure resulting in the selective and predict recognition of biological substrates. The phenomenon of encapsulation was demonstrated in solution by NMR and CD spectroscopy and in the solid state by X-ray diffraction.La reconnaissance molĂ©culaire constitue lâune des questions fondamentales les plus discutĂ©es dans le domaine de la chimie supramolĂ©culaire. Cette thĂšse prĂ©sente la conception, la synthĂšse et lâĂ©tude des propriĂ©tĂ©s de capsules hĂ©licoĂŻdales auto-organisĂ©es par repliement dâoligoamides aromatiques. Ces rĂ©cepteurs sont constituĂ©s dâune chaĂźne oligomĂ©rique se repliant en hĂ©lice et comprenant une sĂ©quence dâunitĂ©s codant pour des diamĂštres diffĂ©rents. Le repliement de lâoligomĂšre donne naissance Ă une cavitĂ© pouvant accueillir des molĂ©cules invitĂ©es. La grande modularitĂ© des sĂ©quences, permettant une Ă©volution contrĂŽlĂ©e des structures des foldamĂšres, donne lieu Ă la reconnaissance sĂ©lective et anticipĂ©e de substrats dâintĂ©rĂȘts biologiques. Le phĂ©nomĂšne dâencapsulation a Ă©tĂ© mis en Ă©vidence en solution par spectroscopie RMN et CD, et dans le solide par diffraction des rayons X
Helical capsules based on aromatic oligoamide foldamers for molecular recognition
La reconnaissance molĂ©culaire constitue lâune des questions fondamentales les plus discutĂ©es dans le domaine de la chimie supramolĂ©culaire. Cette thĂšse prĂ©sente la conception, la synthĂšse et lâĂ©tude des propriĂ©tĂ©s de capsules hĂ©licoĂŻdales auto-organisĂ©es par repliement dâoligoamides aromatiques. Ces rĂ©cepteurs sont constituĂ©s dâune chaĂźne oligomĂ©rique se repliant en hĂ©lice et comprenant une sĂ©quence dâunitĂ©s codant pour des diamĂštres diffĂ©rents. Le repliement de lâoligomĂšre donne naissance Ă une cavitĂ© pouvant accueillir des molĂ©cules invitĂ©es. La grande modularitĂ© des sĂ©quences, permettant une Ă©volution contrĂŽlĂ©e des structures des foldamĂšres, donne lieu Ă la reconnaissance sĂ©lective et anticipĂ©e de substrats dâintĂ©rĂȘts biologiques. Le phĂ©nomĂšne dâencapsulation a Ă©tĂ© mis en Ă©vidence en solution par spectroscopie RMN et CD, et dans le solide par diffraction des rayons X.Molecular recognition is one of the major challenges of supramolecular chemistry. Here, we present the design, synthesis and study of helical capsules properties self-organised by aromatic oligoamide folding. These receptors consist of oligomeric chains that fold into a helical conformation and comprise of a sequence of units which code for different diameters. Oligomeric folding defines a cavity which can recognize guests. The great modularity of the sequences has allowed a controlled evolution of foldamer structure resulting in the selective and predict recognition of biological substrates. The phenomenon of encapsulation was demonstrated in solution by NMR and CD spectroscopy and in the solid state by X-ray diffraction
Helical capsules based on aromatic oligoamide foldamers for molecular recognition
La reconnaissance molĂ©culaire constitue lâune des questions fondamentales les plus discutĂ©es dans le domaine de la chimie supramolĂ©culaire. Cette thĂšse prĂ©sente la conception, la synthĂšse et lâĂ©tude des propriĂ©tĂ©s de capsules hĂ©licoĂŻdales auto-organisĂ©es par repliement dâoligoamides aromatiques. Ces rĂ©cepteurs sont constituĂ©s dâune chaĂźne oligomĂ©rique se repliant en hĂ©lice et comprenant une sĂ©quence dâunitĂ©s codant pour des diamĂštres diffĂ©rents. Le repliement de lâoligomĂšre donne naissance Ă une cavitĂ© pouvant accueillir des molĂ©cules invitĂ©es. La grande modularitĂ© des sĂ©quences, permettant une Ă©volution contrĂŽlĂ©e des structures des foldamĂšres, donne lieu Ă la reconnaissance sĂ©lective et anticipĂ©e de substrats dâintĂ©rĂȘts biologiques. Le phĂ©nomĂšne dâencapsulation a Ă©tĂ© mis en Ă©vidence en solution par spectroscopie RMN et CD, et dans le solide par diffraction des rayons X.Molecular recognition is one of the major challenges of supramolecular chemistry. Here, we present the design, synthesis and study of helical capsules properties self-organised by aromatic oligoamide folding. These receptors consist of oligomeric chains that fold into a helical conformation and comprise of a sequence of units which code for different diameters. Oligomeric folding defines a cavity which can recognize guests. The great modularity of the sequences has allowed a controlled evolution of foldamer structure resulting in the selective and predict recognition of biological substrates. The phenomenon of encapsulation was demonstrated in solution by NMR and CD spectroscopy and in the solid state by X-ray diffraction
Iterative Evolution of an Abiotic Foldamer Sequence for the Recognition of Guest Molecules with Atomic Precision
A synthetic helical aromatic oligoamide foldamer receptor with high affinity and selectivity for tartaric acid was' subjected to a structure-based evolution of its sequence via mutations, additions, and deletions of monomers to produce a new receptor having, high affinity and selectivity for malic acid, a guest that differs from tartaric acid by a single oxygen atom. Seven iteratively modified sequences were synthesized. Detailed structural investigations of host-guest complexes were carried out systematically to guide the design of the next generation. A first outcome was a reversal of selectivity of the receptors, with a starting preference for tartaric acid over malic acid of over 10(2) and an ending sequence showing a preference for malic acid over tartaric acid of over 10(2). Another outcome was a very strong enhancement of the affinity for malic acid, despite the fact that it has fewer recognition features for binding through polar interactions such as hydrogen bonds. Such a level of discrimination between resembling guests exemplifies the amenability of foldamers to outstanding achievements in molecular recognition. Altogether, our results demonstrate the viability of a rational receptor design approach that exploits the modularity of foldamer sequences and, in the case of aromatic amide foldamers, their amenability to structural elucidation, their relative ease of synthesis, and the predictability of their structure
Palladium-Mediated Arylation of Lysine in Unprotected Peptides
A mild method for the arylation of lysine in an unprotected peptide is presented. In the presence of a preformed biarylphosphine-supported palladium(II)âaryl complex and a weak base, lysine amino groups underwent CâN bond formation at room temperature. The process generally exhibited high selectivity for lysine over other amino acids containing nucleophilic side chains and was applicable to the conjugation of a variety of organic compounds, including complex drug molecules, with an array of peptides. Finally, this method was also successfully applied to the formation of cyclic peptides by macrocyclization.National Institutes of Health (U.S.) (Grant R01GM110535
In-solution enrichment identifies peptide inhibitors of proteinâprotein interactions
The use of competitive inhibitors to disrupt proteinâprotein interactions (PPIs) holds great promise for the treatment of disease. However, the discovery of high-affinity inhibitors can be a challenge. Here we report a platform for improving the affinity of peptide-based PPI inhibitors using non-canonical amino acids. The platform utilizes size exclusion-based enrichment from pools of synthetic peptides (1.5â4 kDa) and liquid chromatography-tandem mass spectrometry-based peptide sequencing to identify high-affinity binders to protein targets, without the need for âreporterâ or âencodingâ tags. Using this approachâwhich is inherently selective for high-affinity bindersâwe realized gains in affinity of up to ~100- or ~30-fold for binders to the oncogenic ubiquitin ligase MDM2 or HIV capsid protein C-terminal domain, which inhibit MDM2âp53 interaction or HIV capsid protein C-terminal domain dimerization, respectively. Subsequent macrocyclization of select MDM2 inhibitors rendered them cell permeable and cytotoxic toward cancer cells, demonstrating the utility of the identified compounds as functional PPI inhibitors. Keywords: chemical libraries; chemical tools; peptides; screeningBettencourt Schueller Foundation (Award (LT000745/2014-C)United States. Defense Advanced Research Projects Agency (Award 023504-001)National Institute of General Medical Sciences (U.S.) (Grant 5-R01-GM110535)Laboratoires Servier (Gidy, France) (Award 023504-001
Polar solvent effects on tartaric acid binding by aromatic oligoamide foldamer capsules
International audienceAromatic oligoamide sequences able to fold into single helical capsules were functionalized with two types of side chains to make them be soluble in various solvents such as chloroform, methanol or water and their propensity to recognize tartaric acid was evaluated. Binding affinities to tartaric acid and binding thermodynamics in the different media were investigated by variable temperature 1 H NMR and ITC experiments, the two methods giving consistent results. We show that tartaric acid binding mainly rests on enthalpically favourable polar interactions that were found to be sufficiently strong to be effective in presence of a polar aprotic solvent (DMSO) and even in pure methanol. Binding in water was very low. The stronger binding interactions were found to be more susceptible to the effect of competitive solvents and to be compensated by unfavourable entropic effects. Thus, the best host in less polar medium eventually was found to be the worst host in protic solvents. An interesting case of entropically driven binding was evidenced in methanol
Structure Elucidation of Host-Guest Complexes of Tartaric and Malic Acids by Quasi-Racemic Crystallography
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