RNA represents an extremely promising and yet challenging therapeutic target. Here, we report the design of a series of C-nucleosides as original RNA binders. Some of them bind strongly and ...selectively to A-site prokaryotic ribosomal RNA.
Novel C-nucleosides as selective binders of prokaryotic ribosomal A-site RNA and promising scaffolds for therapeutic RNA targeting.
The human immunodeficiency virus type‐1 (HIV‐1) Tat protein stimulates transcriptional elongation. Tat is involved in the transcription machinery by binding to the transactivation response region ...(TAR) RNA stem‐loop structure, which is encoded by the 5′ leader sequence found in all HIV‐1 mRNAs. Herein, we report the rational design, synthesis, and in vitro evaluation of new RNA binding agents that were conceived in order to bind strongly and selectively to the stem‐loop structure of TAR RNA and, thus, inhibit the Tat/TAR interaction. We have demonstrated that the conjugation of modified nucleobases, able to interact specifically with an RNA base pair, and various amino acids allows these motifs to bind the target RNA selectively and in a cooperative manner that leads to the inhibition of viral replication in HIV‐infected cells.
Kissing interaction: The rational design, synthesis, and in vitro evaluation of new RNA binding agents are reported. The conjugation of an artificial nucleobase, which is able to interact specifically with an RNA base pair (Hoogsteen pairing), and various amino acids leads to efficient binding to the target RNA and the inhibition of viral replication in HIV‐infected cells (see figure).
This work deals with Perfectly Matched Layers (PMLs) in the context of dispersive media, and in particular for Negative Index Metamaterials (NIMs). We first present some properties of dispersive ...isotropic Maxwell equations that include NIMs. We propose and analyse the stability of very general PMLs for a large class of dispersive systems using a new change of variable. We give necessary criteria for the stability of such models that show in particular that the classical PMLs applied to NIMs are unstable and we confirm this numerically. For dispersive isotropic Maxwell equations, this analysis is completed by giving necessary and sufficient conditions of stability. Finally, we propose new PMLs that satisfy these criteria and demonstrate numerically their efficiency.
In this work, we provide a review of recent results on the mathematical analysis of space-time variational bilinear forms associated to transient boundary integral operators for the wave equation. ...Most of the results will be proven directly in the time domain and compared to similar results (most of them obtained in the Laplace domain) that can be found in the literature.
A plasmon as a stimulus opens up new opportunities for selective and regulated "from-surface" polymerization and functionalization of surfaces. Here, the first example of plasmon-assisted ...nitroxide-mediated polymerization (NMP) of stimuli-responsive block copolymers poly(
N
-isopropylacrylamide)-
co
-4-vinylboronic acid is reported. The growth of a polymer film at room temperature was achieved
via
plasmon-induced homolysis of alkoxyamines covalently attached to the surface of plasmon-active gold gratings at room temperature. Control of temperature, finite-difference time-domain method simulation of plasmon intensity distribution shift during polymerization, electron paramagnetic resonance experiments and other assays provide strong support for the plasmon-initiated mechanism of NMP. We demonstrated not only the control of the resulting polymer thickness but also the preparation of a surface-enhanced Raman spectroscopy chip for the detection of glycoproteins as a powerful example of plasmon-assisted NMP potential.
The first method of plasmon-induced nitroxide-mediated polymerization on periodical gold gratings has been developed.
Modeling and simulation of a grand piano
The Journal of the Acoustical Society of America/The journal of the Acoustical Society of America,
07/2013
Journal Article
The nature of plasmon interaction with organic molecules is a subject of fierce discussion about thermal and non-thermal effects. Despite the abundance of physical methods for evaluating the ...plasmonic effects, chemical insight has not been reported yet. In this contribution, we propose a chemical insight into the plasmon effect on reaction kinetics using alkoxyamines as an organic probe through their homolysis, leading to the generation of nitroxide radicals. Alkoxyamines (TEMPO- and SG
1
-substituted) with well-studied homolysis behavior are covalently attached to spherical Au nanoparticles. We evaluate the kinetic parameters of homolysis of alkoxyamines attached on a plasmon-active surface under heating and irradiation at a wavelength of plasmon resonance. The estimation of kinetic parameters from experiments with different probes (
Au-TEMPO
,
Au-SG
1
,
Au-SG
1
-TEMPO
) allows revealing the apparent differences associated with the non-thermal contribution of plasmon activation. Moreover, our findings underline the dependency of kinetic parameters on the structure of organic molecules, which highlights the necessity to consider the nature of organic transformations and molecular structure in plasmon catalysis.
Kinetic study of alkoxyamine homolysis revealed the impact of non-thermal effects in plasmon-assisted reactions.
The emergence and spread of drug-resistant
parasites shed a serious concern on the worldwide control of malaria, the most important tropical disease in terms of mortality and morbidity. This ...situation has led us to consider the use of peptide-alkoxyamine derivatives as new antiplasmodial prodrugs that could potentially be efficient in the fight against resistant malaria parasites. Indeed, the peptide tag of the prodrug has been designed to be hydrolysed by parasite digestive proteases to afford highly labile alkoxyamines drugs, which spontaneously and instantaneously homolyse into two free radicals, one of which is expected to be active against
. Since the parasite enzymes should trigger the production of the active drug in the parasite's food vacuoles, our approach is summarized as "to dig its grave with its fork". However, despite promising sub-micromolar IC
values in the classical chemosensitivity assay, more in-depth tests evidenced that the anti-parasite activity of these compounds could be due to their cytostatic activity rather than a truly anti-parasitic profile, demonstrating that the antiplasmodial activity cannot be based only on measuring antiproliferative activity. It is therefore imperative to distinguish, with appropriate tests, a genuinely parasiticidal activity from a cytostatic activity.
The local surface plasmon resonances of gold nanoparticles have the potential to create alternative pathways for organic chemical reactions. These transformations depend on various physical factors, ...such as the temperature, illumination regime, and nanoparticle type. However, the role of chemical factors associated with organic reactants, including the molecular structure, electronic effects, and bonding with the metal surface, is often underestimated. To explore the role of these chemical factors, we synthesized five alkoxyamines (AAs) with different chemical and electronic structures and used electron paramagnetic resonance spectroscopy to study the kinetics of plasmon-induced homolysis. The kinetic data revealed that the rate constant (k d) for plasmon-assisted homolysis is dependent on the highest occupied molecular orbital (HOMO) energy of the AAs, which cannot be described by the kinetic parameters or activation energies observed in thermal homolysis experiments. The proximity of the HOMO to the Fermi energy (E f) of Au led to a more active decrease in the energy required to excite the adsorbate. The observed trend in k d indicates that the intramolecular excitation mechanism plays a key role instead of other commonly accepted mechanisms, which is supported by DFT calculations, spectroscopic characterization, and numerous control experiments. The intramolecular excitation mechanism is the most relevant explanation for the plasmon-induced homolysis of AAs. This observation suggests that the electronic structures of the organic molecules may play a key role in other related reactions used to study the mechanisms of plasmon catalysis.
When solving 2D linear elastodynamic equations in homogeneous isotropic media, a Helmholtz decomposition of the displacement field decouples the equations into two scalar wave equations that only ...interact at the boundary. It is then natural to look for numerical schemes that independently solve the scalar equations and couple the solutions at the boundary. The case of rigid boundary condition was treated by Burel Ph.D. thesis, Université Paris Sud-Paris XI (2014) and Burel et al. Numer. Anal. Appl. 5 (2012), pp. 136–143. However the case of traction free boundary condition was proven by Martinez et al. J. Sci. Comput. 77 (2018), pp. 1832–1873 to be unstable if a straightforward approach is used. Then an adequate functional framework as well as a time domain mixed formulation to circumvent these issues was presented. In this work we first review the formulation presented by Martinez et al. J. Sci. Comput. 77 (2018), pp. 1832–1873 and propose a subsequent discretised formulation. We provide the complete stability analysis of the corresponding numerical scheme. Numerical results that illustrate the theory are also shown.
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