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. 相似文献
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.
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. 相似文献
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. 相似文献
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).相似文献
We list all possible dim = 6 CP conserving and SU(3) × SU(2) × U(1) gauge invariant interactions, which could be generated in case no new particles would be reachable in the future Colliders, and the only observable New Physics would be in the form of new interactions affecting the scalar sector and the quarks of the third family. These interactions are described by operators involving the standard model scalar field, the quarks of the third family and the gauge bosons. Subsequently, we identify those operators which do not contribute to LEP1 (and lower energy) observables at tree level and are not purely gluonic. Since present measurements do not strongly constrain the couplings of these operators, we derive here the unitarity bounds on them. Finally, in order to get a feeling on the possible physical meaning of the appearance of any of these operators, we identify the operators generated in a class of renormalizable dynamical models which at the TeV scale, are fully described by the SU(3) × SU(2) × U(1) gauge group. 相似文献