Protein ligand design: from phage display to synthetic protein epitope mimetics in human antibody Fc-binding peptidomimetics

Phage display is a powerful method for selecting peptides with novel binding functions. Synthetic peptidomimetic chemistry is a powerful tool for creating structural diversity in ligands as a means to establish structure-activity relationships. Here we illustrate a method of bridging these two methodologies, by starting with a disulfide bridged phage display peptide which binds a human antibody Fc fragment (Delano et al. Science 2000, 287, 1279) and creating a backbone cyclic beta-hairpin peptidomimetic with 80-fold higher affinity for the Fc domain. The peptidomimetic is shown to adopt a well-defined beta-hairpin conformation in aqueous solution, with a bulge in one beta-strand, as seen in the crystal structure of the phage peptide bound to the Fc domain. The higher binding affinity of the peptidomimetic presumably reflects the effect of constraining the free ligand into the conformation required for binding, thus highlighting in this example the influence that ligand flexibility has on the binding energy. Since phage display peptides against a wide variety of different proteins are now accessible, this approach to synthetic ligand design might be applied to many other medicinally and biotechnologically interesting target proteins.     

Preparation of Clickable Poly(3‐hydroxyalkanoate) (PHA): Application to Poly(ethylene glycol) (PEG) Graft Copolymers Synthesis

A new synthesis of amphiphilic biodegradable copolymers consisting of hydrophobic poly(3‐hydroxyalkanoate) (PHA) backbone and hydrophilic poly(ethylene glycol) (PEG) units as side chains is described. Poly[(3‐hydroxyoctanoate)‐co‐(3‐hydroxyundecenoate)] (PHOU) was first methanolyzed and its unsaturated side chains were quantitatively oxidized to carboxylic acid. Esterification with propargyl alcohol led to an alkyne‐containing “clickable” PHA in 71% conversion. Its reactivity was successfully demonstrated by grafting azide‐terminated PEG chains of 550 and 5 000 g · mol⁻¹, respectively. All products were fully characterized using GPC, ¹H, and COSY NMR.

     

AgInS2–ZnS nanocrystals: Evidence of bistable states using light‐induced electron paramagnetic resonance and photoluminescence

The precursor (AgIn)_x Zn_2(1–x)(S₂CN(C₂H₅)₂)₄ was used to prepared AgInS₂–ZnS nanocrystals with different compositions (x = 0.4 and x = 0.7) and with different time of reaction (10 min and 75 min). The photoluminescence features of the nanocrystals were addressed by combining steady‐state spectroscopy and light‐induced electron paramagnetic resonance. Both techniques showed the contribution of at least two components for the emission, previously assigned to surface and intrinsic states. Light‐induced electron paramagnetic resonance allowed detection of the photocreation both of irreversible paramagnetic species that are likely responsible for the nano‐crystals degradation assigned to surface states and of reversible paramagnetic species assigned to intrinsic states. Moreover, reversible bistable paramagnetic states were observed. This Letter provides a scheme that might be useful in addressing the well‐known problem of aging of the nanocrystals. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Worst-case analysis for flow shop scheduling problems with an exponential learning effect

A real industrial production phenomenon, referred to as learning effects, has drawn increasing attention. However, most research on this issue considers only single machine problems. Motivated by this limitation, this paper considers flow shop scheduling problems with an exponential learning effect. By the exponential learning effect, we mean that the processing time of a job is defined by an exponent function of its position in a processing permutation. The objective is to minimize one of the four regular performance criteria, namely, the total completion time, the total weighted completion time, the discounted total weighted completion time, and the sum of the quadratic job completion times. We present heuristic algorithms by using the optimal permutations for the corresponding single-machine scheduling problems. We also analyse the worst-case bound of our heuristic algorithms.     

Three Dimensionality and Orbital Characters of the Fermi Surface in (Tl,Rb)_{y}Fe_{2-x}Se_{2}

We report a comprehensive angle-resolved photoemission spectroscopy study of the tridimensional electronic bands in the recently discovered Fe selenide superconductor (Tl,Rb)_{y}Fe_{2-x}Se_{2} (T_{c}=32 K). We determined the orbital characters and the k_{z} dependence of the low energy electronic structure by tuning the polarization and the energy of the incident photons. We observed a small 3D electron Fermi surface pocket near the Brillouin zone center and a 2D like electron Fermi surface pocket near the zone boundary. The photon energy dependence, the polarization analysis and the local-density approximation calculations suggest a significant contribution from the Se 4p_{z} and Fe 3d_{xy} orbitals to the small electron pocket. We argue that the emergence of Se 4p_{z} states might be the cause of the different magnetic properties between Fe chalcogenides and Fe pnictides.     

Poly(3-hydroxyalkanoate)-derived amphiphilic graft copolymers for the design of polymersomes

Amphiphilic graft copolymers composed of biocompatible bacterial poly(3-hydroxyalkanoate) and poly(ethylene glycol) have been synthesized by thiol-ene addition. They were demonstrated to form well-defined nanoscale vesicles in water by cryo-transmission electron microscopy.     

An Efficient Thiol‐Ene Chemistry for the Preparation of Amphiphilic PHA‐Based Graft Copolymers

We present a straightforward method to prepare amphiphilic graft copolymers consisting of hydrophobic poly(3‐hydroxyalkanoates) (PHAs) backbone and hydrophilic α‐amino‐ω‐methoxy poly(oxyethylene‐co‐oxypropylene) (Jeffamine®) units. Poly(3‐hydroxyoctanoate)‐co‐(3‐hydroxyundecenoate) (PHOU) was first methanolyzed to obtain the desired molar mass. The amino end groups of Jeffamine were converted into thiol by a reaction with N‐acetylhomocysteine thiolactone and subsequently photografted. This “one‐pot” functionalization prevents from arduous and time‐consuming functionalization of the hydrophilic precursor or tedious modifications of PHAs, thus simplifying the process. The amphiphilic nature of modified PHAs leads to water‐soluble copolymers exhibiting thermoresponsive behavior.     

How Well Do We Handle the Sample Preparation,FT-ICR Mass Spectrometry Analysis,and Data Treatment of Atmospheric Waters?

FT-ICR MS (Fourier-transform ion cyclotron resonance mass spectrometry) analysis has shown great potential to aid in the understanding of the extremely high molecular diversity of cloud water samples. The main goal of this work was to determine the differences in terms of formula assignment for analytical (i.e., measurement replicates) and experimental replicates of a given cloud water sample. The experimental replicates, obtained by solid phase extraction, were also compared to the results obtained for freeze-dried samples to evaluate whether the presence of salts interferes with the analysis. Two S/N ratios, generally adopted for atmospheric samples, were evaluated, and three different algorithms were used for assignment: DataAnalysis 5.3 (Bruker), Composer (Sierra Analytics), and MFAssignR (Chemical Advanced Resolution Methods Lab). In contrast to other works, we wanted to treat this comparison from the point of view of users, who usually must deal with a simple list of m/z ratios and intensity with limited access to the mass spectrum characteristics. The aim of this study was to establish a methodology for the treatment of atmospheric aqueous samples in light of the comparison of three different software programs, to enhance the possibility of data comparison within samples.     

A quasi-optimal convergence result for fracture mechanics with XFEM

The aim of this Note is to give a convergence result for a variant of the eXtended Finite Element Method (XFEM) on cracked domains using a cut-off function to localize the singular enrichment area. The difficulty is caused by the discontinuity of the displacement field across the crack, but we prove that a quasi-optimal convergence rate holds in spite of the presence of elements cut by the crack. The global linear convergence rate is obtained by using an enriched linear finite element method. To cite this article: E. Chahine et al., C. R. Acad. Sci. Paris, Ser. I 342 (2006).