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91.
Luca Mazzei Michele Cianci Stefano Benini Stefano Ciurli 《Chemistry (Weinheim an der Bergstrasse, Germany)》2019,25(52):12145-12158
Urease uses a cluster of two NiII ions to activate a water molecule for urea hydrolysis. The key to this unsurpassed enzyme is a change in the conformation of a flexible structural motif, the mobile flap, which must be able to move from an open to a closed conformation to stabilize the chelating interaction of urea with the NiII cluster. This conformational change brings the imidazole side chain functionality of a critical histidine residue, αHis323, in close proximity to the site that holds the transition state structure of the reaction, facilitating its evolution to the products. Herein, we describe the influence of the solution pH in modulating the conformation of the mobile flap. High-resolution crystal structures of urease inhibited in the presence of N-(n-butyl)phosphoric triamide (NBPTO) at pH 6.5 and pH 7.5 are described and compared to the analogous structure obtained at pH 7.0. The kinetics of urease in the absence and presence of NBPTO are investigated by a calorimetric assay in the pH 6.0–8.0 range. The results indicate that pH modulates the protonation state of αHis323, which was revealed to have pKa=6.6, and consequently the conformation of the mobile flap. Two additional residues (αAsp224 and αArg339) are shown to be key factors for the conformational change. The role of pH in modulating the catalysis of urea hydrolysis is clarified through the molecular and structural details of the interplay between protein conformation and solution acidity in the paradigmatic case of a metalloenzyme. 相似文献
92.
Benedict Vasco Normenyo Florian Luca Alain Togbé 《Periodica Mathematica Hungarica》2018,77(2):318-328
In this paper, all base 10 repdigits expressible as sums of three Pell numbers are found. 相似文献
93.
We study a question of Erd?s and Graham on products of factorials being a square or again a factorial. 相似文献
94.
Synthesis and Biological Evaluation of RGD Peptidomimetic–Paclitaxel Conjugates Bearing Lysosomally Cleavable Linkers
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Alberto Dal Corso Dr. Michele Caruso Dr. Laura Belvisi Dr. Daniela Arosio Prof. Dr. Umberto Piarulli Dr. Clara Albanese Dr. Fabio Gasparri Dr. Aurelio Marsiglio Dr. Francesco Sola Dr. Sonia Troiani Dr. Barbara Valsasina Dr. Luca Pignataro Dr. Daniele Donati Prof. Dr. Cesare Gennari 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(18):6921-6929
Two small‐molecule–drug conjugates (SMDCs, 6 and 7 ) featuring lysosomally cleavable linkers (namely the Val–Ala and Phe–Lys peptide sequences) were synthesized by conjugation of the αvβ3‐integrin ligand cyclo[DKP–RGD]‐CH2NH2 ( 2 ) to the anticancer drug paclitaxel (PTX). A third cyclo[DKP–RGD]–PTX conjugate with a nonpeptide “uncleavable” linker ( 8 ) was also synthesized to be tested as a negative control. These three SMDCs were able to inhibit biotinylated vitronectin binding to the purified αVβ3‐integrin receptor at nanomolar concentrations and showed good stability at pH 7.4 and pH 5.5. Cleavage of the two peptide linkers was observed in the presence of lysosomal enzymes, whereas conjugate 8 , which possesses a nonpeptide “uncleavable” linker, remained intact under these conditions. The antiproliferative activities of the conjugates were evaluated against two isogenic cell lines expressing the integrin receptor at different levels: the acute lymphoblastic leukemia cell line CCRF‐CEM (αVβ3?) and its subclone CCRF‐CEM αVβ3 (αVβ3+). Fairly effective integrin targeting was displayed by the cyclo[DKP–RGD]–Val–Ala–PTX conjugate ( 6 ), which was found to differentially inhibit proliferation in antigen‐positive CCRF‐CEM αVβ3 versus antigen‐negative isogenic CCRF‐CEM cells. The total lack of activity displayed by the “uncleavable” cyclo[DKP–RGD]–PTX conjugate ( 8 ) clearly demonstrates the importance of the peptide linker for achieving the selective release of the cytotoxic payload. 相似文献
95.
Massimiliano Berti Luca Biasco Michela Procesi 《Archive for Rational Mechanics and Analysis》2014,212(3):905-955
We prove the existence of Cantor families of small amplitude, analytic, linearly stable quasi-periodic solutions of reversible derivative wave equations. 相似文献
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99.
Johnny Henderson Rodica Luca 《NoDEA : Nonlinear Differential Equations and Applications》2013,20(3):1035-1054
We investigate the existence and multiplicity of positive solutions of multi-point boundary value problems for systems of nonlinear higher-order ordinary differential equations. 相似文献
100.
Luca Deseri Mario Di Paola Massimiliano Zingales 《International Journal of Solids and Structures》2014
Complex materials, often encountered in recent engineering and material sciences applications, show no complete separations between solid and fluid phases. This aspect is reflected in the continuous relaxation time spectra recorded in cyclic load tests. As a consequence the material free energy cannot be defined in a unique manner yielding a significative lack of knowledge of the maximum recoverable work that can extracted from the material. The non-uniqueness of the free energy function is removed in the paper for power-laws relaxation/creep function by using a recently proposed mechanical analogue to fractional-order hereditariness. 相似文献