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91.
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We have developed a structure-based approach to the design of protein ligands. This approach is based on the transfer of a functional binding motif of amino acids, often referred as to the "hot spot", on a host protein able to reproduce the functional topology of these residues. The scaffolds were identified by a systematic in silico search in the Protein Data Bank for proteins possessing a group of residues in a topology similar to that adopted by the functional motif in a reference ligand of known 3D structure. In contrast to previously reported studies, this search is independent of the particular secondary structure supporting the functional motif. To take into account the global properties of the host protein, two additional criteria were taken into account in the selection process: (1) Only those scaffolds sterically compatible with the positioning of the functional motif as observed in a reference complex model were retained. (2) Host proteins displaying electrostatic potentials, in the region of the transferred functional motif, similar to that of the reference ligand were selected. This approach was applied to the development of protein ligands of the Kv1.2 channel using BgK, a small protein isolated from the sea anemone Bunodosoma granulifera, as the reference ligand. Four proteins obtained by this approach were produced for experimental evaluation. The X-ray structure of one of these proteins was determined to check for similarity of the transferred functional motif with the structure it adopts in the reference ligand. Three of these protein ligands bind the Kv1.2 channel with inhibition constants of 0.5, 1.5, and 1.6 microM. Several mutants of these designed protein ligands gave binding results consistent with the presumed binding mode. These results show that protein ligands can be designed by transferring a binding motif on a protein host selected to reproduce the functional topology of this motif, irrespective to the secondary structure supporting the functional motif, if the host protein possesses steric and electrostatic properties compatible with the binding to the target. This result opens the way to the design of protein ligands by taking advantage of the considerable structural repertoire of the Protein Data Bank.  相似文献   
94.
Highly ordered self-assembled multi-layer structures with denatured collagen wrapped single wall carbon nanotubes and surfactant systems were obtained through bioinspired methodology.  相似文献   
95.
Radio LANs are emerging in the computing world. They are supported by distinct configurations: on the one hand radio LANs with base stations and a wired backbone, on the other hand radio LANs implementing Intra-forwarding. Adding a new node in a radio LAN with Intra-forwarding, increases the reliability, while this reliability decreases with ad hoc or hub configurations. This advantage of Intra-forwarding is quantified. Intra-forwarding, as defined in the HIPERLAN standard, is based on a hop-by-hop policy and link check procedures. It is shown how point-to-point packets and broadcast packets are forwarded. The three basic components of Intra-forwarding needed to build and update the Intra-forwarding database are described. The originality of this approach is the use of multipoint relays which enable better scalability. The correctness of the Intra-forwarding protocol is proved and its cost is evaluated.  相似文献   
96.
The use of K-normed spaces gives us the possibility to prove that a fixed point theorem due to B. Luo is equivalent to the Banach Contraction Principle. This confirms the conspiracy among fixed point theorems. Moreover the theorem of Lou is improved and extended to different contexts. A counterexample about the fixed points of the sum of a contraction and an integral operator is given. The usefulness of K-norm is tested on a Volterra integral equation as well.

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97.
Building on the method of Kantorovich majorants, we give convergence results and error estimates for the two-step Newton method for the approximate solution of a nonlinear operator equation.  相似文献   
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99.
Lithium amides react with vinylferrocene in the presence of TMEDA to provide the corresponding (2-aminoethyl)ferrocenes in good to excellent yields. A range of secondary amines can be employed in this amidolithiation reaction, with cyclic derivatives affording particularly good yields of the 2-aminoethyl-substituted ferrocene product. This operationally simple procedure provides one of the most straightforward routes to this class of mono-substituted ferrocene.  相似文献   
100.
The synthesis of a building block containing the photobiologically relevant cis-syn thymine cyclobutane photoproduct and its incorporation into oligonucleotides by the phosphoramidite-based solid-phase synthesis is reported. Compared to previous syntheses, this route is extremely short and allows such modified oligonucleotides to be easily available for biological studies.  相似文献   
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