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1.
Synthesis and Biological Evaluation of RGD Peptidomimetic–Paclitaxel Conjugates Bearing Lysosomally Cleavable Linkers 下载免费PDF全文
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
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Francescamaria Donati Piero Boraschi Roberto Gigoni Simonetta Salemi Fabio Falaschi Carlo Bartolozzi 《Magnetic resonance imaging》2013
Purpose
To present diffusion and perfusion magnetic resonance imaging (MRI) characteristics of focal nodular hyperplasia (FNH) of the liver.Materials and Methods
Thirty-five patients with 52 FNHs (21 were pathologically-confirmed) underwent MRI at 1.5-T device. MR diffusion [diffusion-weighted imaging (DWI)] was performed using a free-breathing single-shot, spin-echo, echo-planar sequence with b gradient factor value of 500 s/mm². MR perfusion [perfusion-weighted imaging (PWI)] consisted of a 3D free-breathing LAVA sequence repeated up to 5 minutes after injection of 7 mL Gd-BOPTA (MultiHance, Bracco, Italy) and 20 mL saline flush at a flow rate of 4 mL/s. Apparent diffusion coefficient (ADC) and time-signal intensity curve (TSIC) were obtained for both normal liver and each FNH by two reviewers in conference; maximum enhancement (ME) percentage, time to peak enhancement (TTP), and maximal slope (MS) were also calculated.Results
On DWI mean ADC value was 1.624×10− 3 mm2/s for normal liver and 1.629×10− 3 mm2/s for FNH. ADC value for each FNH and the normal liver was not statistically different (P= .936). On PWI, TSIC-Type 1 (quick and marked enhancement and quick decay followed by slowly decaying) was observed in all 52 FNHs, and TSIC-Type 2 (fast enhancement followed by slowly decaying plateau) in all normal livers. The mean ME, TTP and MS values were significantly different for FNH and normal liver (P= .005).Conclusion
FNHs of the liver showed typical diffusion and perfusion MRI characteristics in all cases. On the ADC map, we could get similar value between the FNHs and the background parenchyma. On the perfusion imaging, FNHs showed a different pattern distinguished from the background liver. 相似文献4.
Giorgio Donati Nicola Durante Alessandro Siciliano 《Designs, Codes and Cryptography》2014,72(1):135-139
The linear collineation group of a classical unital of $\mathrm{PG}(2,q^2)$ contains a group of homologies of order $q+1$ . In this paper we prove that if $\mathcal{U }$ is a unital of PG $(2,q^2)$ stabilized by a homology group of order $q+1$ and $q$ is a prime number, then $\mathcal{U }$ is classical. 相似文献
5.
The growth of Fe on Au(111) at 300 K in the sub-monolayer regime has been investigated using scanning tunneling microscopy, focusing on the mechanisms of nucleation, coalescence and interlayer diffusion. Below a coverage of 0.1 ML, Fe growth proceeds in a well-ordered fashion producing regular arrays of islands, while approaching the island coalescence threshold (above 0.35–0.4 ML), we observed a consistent increasing of random island nucleation. These observations have been interpreted through rate equation models for the island densities in the presence of preferred nucleation sites. The evolution of the second layer fraction has also been interpreted in a rate equation scheme. Our results show that the ordered to random growth transition can be explained by including in the model bond breaking mechanisms due to finite Fe–Fe bond energy. A moderate interlayer diffusion has been inferred from data analysis between the second and the first layer, which has been used to estimate the energy barrier of the adatoms descending process. 相似文献
6.
Fabio RD Alvaro G Bertani B Donati D Giacobbe S Marchioro C Palma C Lynn SM 《The Journal of organic chemistry》2002,67(21):7319-7328
To prepare in multigram scale new antagonists of the glycine binding site associated to the NMDA receptor, an efficient distereoselective route was set up. The addition of suitable allyltin reagents to chiral N-aryl alpha-imino esters (R-(+)-tert-butyl lactate used as chiral auxiliary), gave the corresponding alpha amino acid-type derivative in high chemical yield and optical purity. This allylation reaction represents a novel example of efficient long-range stereodifferentiation process. In the last part of the synthesis, a regioselective Heck-type cyclization reaction enabled preparation of the target tetrasubstituted exocycle and trisubtituted endocycle double bond derivatives. 相似文献
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8.
Donati C Glotzer SC Poole PH Kob W Plimpton SJ 《Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics》1999,60(3):3107-3119
Using extensive molecular dynamics simulations of an equilibrium, glass-forming Lennard-Jones mixture, we characterize in detail the local atomic motions. We show that spatial correlations exist among particles undergoing extremely large ("mobile") or extremely small ("immobile") displacements over a suitably chosen time interval. The immobile particles form the cores of relatively compact clusters, while the mobile particles move cooperatively and form quasi-one-dimensional, stringlike clusters. The strength and length scale of the correlations between mobile particles are found to grow strongly with decreasing temperature, and the mean cluster size appears to diverge near the mode-coupling critical temperature. We show that these correlations in the particle displacements are related to equilibrium fluctuations in the local potential energy and local composition. 相似文献
9.
C. Rossi C. Bonechi S. Martini M. Ricci G. Corbini P. Corti A. Donati 《Magnetic resonance in chemistry : MRC》2001,39(8):457-462
Proton NMR selective and non-selective spin–lattice relaxation rate measurements were used to monitor the strength of the overall complexation behaviour of a ligand (carbamazepine) toward a macromolecular receptor (albumin). The ‘affinity index,’ a quantitative parameter related to the strength of the ligand–macromolecule interaction, was determined from the experimental contribution of the bound ligand molar fraction to the observed selective spin–lattice relaxation rate. The effect of a second ligand (lamotrigine) on the carbamazepine–albumin interaction was also investigated and was found to have a modulation effect on the carbamazepine–albumin interaction. Copyright © 2001 John Wiley & Sons, Ltd. 相似文献
10.
Let A and B be two points of \(\mathop {\mathrm{PG}}(d,q^n)\) and let \(\Phi \) be a collineation between the stars of lines with vertices A and B, that does not map the line AB into itself. In this paper we prove that if \(d=2\) or \(d\ge 3\) and the lines \(\Phi ^{-1}(AB), AB, \Phi (AB) \) are not in a common plane, then the set \(\mathcal{C}\) of points of intersection of corresponding lines under \(\Phi \) is the union of \(q-1\) scattered \({\mathbb {F}}_{q}\)-linear sets of rank n together with \(\{A,B\}\). As an application we will construct, starting from the set \(\mathcal{C}\), infinite families of non-linear \((d+1, n, q;d-1)\)-MRD codes, \(d\le n-1\), generalizing those recently constructed in Cossidente et al. (Des Codes Cryptogr 79:597–609, 2016) and Durante and Siciliano (Electron J Comb, 2017). 相似文献