Micelles of lipid-oligonucleotide conjugates: implications for membrane anchoring and base pairing

This report examines the organization properties of new fluorescent DNA-lipids, either alone in water or in interaction with 1-octyl-beta-d-glucopyranoside micelles or egg phosphatidylcholine vesicles. We first describe the design and the syntheses of the conjugates. Then, we use UV-Vis absorption, steady-state fluorescence emission, electron microscopy, and fluorescence correlation spectroscopy after two-photon excitation to show that these DNA-lipids form spherical micelles in aqueous solution and incorporate much better in micelles than in vesicles. We also investigate the significance of the lipophilic chains of these DNA-lipids on the melting behavior of the double-stranded hybrids: in water melting curves are broadened whereas in amphiphilic assemblies duplexes melt as the unconjugated controls. This work is expected to be useful for improving the rational design of antisense medicines.     

Reactant concentrations from fluorescence correlation spectroscopy with tailored fluorescent probes. An example of local calibration-free pH measurement

The present account is concerned with the measurement of local reactant concentrations by observing specific fluorescent probes in fluorescence correlation spectroscopy (FCS). The Theoretical Analysis section revisits the photophysical, thermodynamic, and kinetic information that is contained in the corresponding FCS correlation curves. In particular, we examine the conditions under which FCS is revealed as a superior tool to measure concentrations of reactive species. Careful molecular engineering of the specific fluorescent probes that simultaneously integrates photophysical, thermodynamic, and kinetic constraints will be required to benefit most from FCS. We illustrate the FCS titration approach with a series of fluorescent probes that we tailored to measure pH at around 4-6 by FCS after two-photon excitation. We show that an optimal design allows one to access pH without any preliminary calibrations such as the determination of the protonation constant or the photophysical properties of the fluorescent probe.     

Stochastic resonance to control diffusive motion in chemistry

This paper reports on a novel procedure to tune the effective diffusion coefficient of a field-sensitive reactant in the presence of a periodic external field. We investigate the motion of two negatively charged azo dyes interacting with alpha-cyclodextrin (alpha-CD) upon action of a periodic square wave electrical field. We show that the dyes exhibit an effective diffusion coefficient D(eff) that depends on the rate constants for dye complexation within alpha-CD, the period and the amplitude of the field. UV-vis absorption, gradient field (1)H NMR, and fluorescence correlation spectroscopy (FCS) after two photon excitation are used to evidence that D(eff) may be increased far beyond its intrinsic value when specific relations interpreted as a stochastic resonance are fulfilled. The present results may find useful applications in chemical kinetics as well as for molecular sorting.     

The determination of the absolute configuration of tri-o-thymotide by crystal structure analysis and optical rotation.

The absolute configuration of tri-o-thymotide was obtained from the crystal structure of the solvate with (R)-2-butanol in association with optical measurements.     

Sur une cause d'erreur dans le dosage par voie humide de l'azote dans les aciers speciaux

The estimation of nitrogen in normal or special steels by the Kjeldahl method can give results that are too high if the acid used to dissolve the steel (even “pro analysi” acid) contains impurities such as nitrates, and if the metal itself contains even negligible amounts of molybdenum (e g a few ten-thousandths). In this case the blank test can nevertheless give a very weak or negative result.In order to ascertain from this point of view the quality of the acid used, it is necessary to compare the nitrogen contents obtained on a sample with a very low nitrogen content, e g electrolytic iron, in the absence or in the presence, respectively, of a minute addition (about 0.1%) of molybdenum. The difference between these determinations should be negligible. If it is not, then the acid tested should be rejected, or distilled before use.     

Controlled assembly of covalent and supramolecular chemical modules: from engineering of complex structures to high-performance chromatography

A biological approach to generating complex behaviors in chemistry is described. It is suggested theoretically that the assembly of modules composed of chemical reactions or molecular structures under appropriate external constraints can lead to features typical of the biological world like autocatalysis, kinetic proofreading, or oriented molecular motion. This approach may account for the primitive steps of molecular evolution and, in addition, it can find useful applications in chemistry such as high-performance chromatography.     

A General Strategy to Access Structural Information at Atomic Resolution in Polyglutamine Homorepeats

Homorepeat (HR) proteins are involved in key biological processes and multiple pathologies, however their high‐resolution characterization has been impaired due to their homotypic nature. To overcome this problem, we have developed a strategy to isotopically label individual glutamines within HRs by combining nonsense suppression and cell‐free expression. Our method has enabled the NMR investigation of huntingtin exon1 with a 16‐residue polyglutamine (poly‐Q) tract, and the results indicate the presence of an N‐terminal α‐helix at near neutral pH that vanishes towards the end of the HR. The generality of the strategy was demonstrated by introducing a labeled glutamine into a pathological version of huntingtin with 46 glutamines. This methodology paves the way to decipher the structural and dynamic perturbations induced by HR extensions in poly‐Q‐related diseases. Our approach can be extended to other amino acids to investigate biological processes involving proteins containing low‐complexity regions (LCRs).