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91.
Thommey P. Thomas Seok Ki Choi Ming-Hsin Li Alina Kotlyar James R. Baker 《Bioorganic & medicinal chemistry letters》2010,20(17):5191-5194
This communication describes the synthesis and in vitro biological evaluation of novel generation 5 PAMAM dendrimers conjugated with riboflavin as a targeting ligand. Cell-based experiments demonstrated that a dendrimer conjugated with riboflavin is able to undergo cellular binding and uptake in KB cells, and when the dendrimer is also conjugated with methotrexate, the riboflavin dendrimer conjugate can potently inhibit cell growth. 相似文献
92.
Thommey P. Thomas Baohua Huang Ankur Desai Hong Zong Xue-min Cheng Alina Kotlyar Pascale R. Leroueil Thomas Dunham Abraham van der Spek Brent B. Ward James R. Baker 《Bioorganic & medicinal chemistry letters》2010,20(21):6250-6253
Two morphine prodrugs (‘PDA’ and ‘PDB’) were synthesized and the kinetics of esterase-mediated morphine release from these prodrugs were determined when incubated with plasma from different animal species. Morphine was rapidly released from PDA by all species plasma with the maximum reached within 5–10 min; the released morphine was biologically active as determined by an in vitro cAMP assay. The morphine was released from PDB at a slower and species-dependent rate (mouse > rat > guinea pig > human). Morphine’s release from PDB appeared to be mediated by carboxyl esterases as the release was inhibited by the carboxyl esterase inhibitor benzil. PDA nor PDB induce cytotoxicity in the neuronal cell lines SK-NSH and SH-SY5Y. The carboxyl and amino functional moieties present on the linker portions of PDA and PDB, respectively, may facilitate their conjugation to nanoparticles to tailor morphine pharmacokinetics and specific targeting. These studies suggest the potential clinical utility of these prodrugs for morphine release at desired rates by administration of their mixture at selected ratios. 相似文献
93.
Sławomir Tubek Andrzej Bunio Renata Szyguła Alina Tubek 《Biological trace element research》2010,133(3):243-250
The content of elements in rainwater is an indirect indicator of its occurrence in air dust. This is sometimes referred to
as rain fallout and is investigated in applied environmental pollution monitoring schemes. The annual content of elements
in rainwater may be recognized as good index for assessing influence of those environmental factors on human body. The possible
relationship between the concentrations of selected elements in rainwater and the frequency of hospitalization by reason of
angina pectoris, stroke, and peripheral venous thrombosis was investigated in the Opole Voivodship (Poland) area during the
period 2000–2002. There is a relatively high or partly significant correlation between frequency of hospitalization by reason
of these conditions and content of lead, cadmium, chromium, zinc, and chloride in rainwater. Significant gender-dependent
differences were observed only in peripheral venous thrombosis, where important correlations with lead, cadmium, and chromium
were found only in men. 相似文献
94.
Alina Kuzniacka Jolanta Wierzba Magdalena Ratajska Beata S. Lipska Magdalena Koczkowska Monika Malinowska Janusz Limon 《Journal of applied genetics》2013,54(1):27-33
Cornelia de Lange syndrome (CdLS) is a rare multi-system genetic disorder characterised by growth and developmental delay, distinctive facial dysmorphism, limb malformations and multiple organ defects. The disease is caused by mutations in genes responsible for the formation and regulation of cohesin complex. About half of the cases result from mutations in the NIPBL gene coding delangin, a protein regulating the initialisation of cohesion. To date, approximately 250 point mutations have been identified in more than 300 CdLS patients worldwide. In the present study, conducted on a group of 64 unrelated Polish CdLS patients, 25 various NIPBL sequence variants, including 22 novel point mutations, were detected. Additionally, large genomic deletions on chromosome 5p13 encompassing the NIPBL gene locus were detected in two patients with the most severe CdLS phenotype. Taken together, 42 % of patients were found to have a deleterious alteration affecting the NIPBL gene, by and large private ones (89 %). The review of the types of mutations found so far in Polish patients, their frequency and correlation with the severity of the observed phenotype shows that Polish CdLS cases do not significantly differ from other populations. 相似文献
95.
Asaminew H. Aytenfisu Joseph A. Liberman Joseph E. Wedekind David H. Mathews 《RNA (New York, N.Y.)》2015,21(11):1898-1907
Riboswitches are RNA molecules that regulate gene expression using conformational change, affected by binding of small molecule ligands. A crystal structure of a ligand-bound class II preQ1 riboswitch has been determined in a previous structural study. To gain insight into the dynamics of this riboswitch in solution, eight total molecular dynamic simulations, four with and four without ligand, were performed using the Amber force field. In the presence of ligand, all four of the simulations demonstrated rearranged base pairs at the 3′ end, consistent with expected base-pairing from comparative sequence analysis in a prior bioinformatic analysis; this suggests the pairing in this region was altered by crystallization. Additionally, in the absence of ligand, three of the simulations demonstrated similar changes in base-pairing at the ligand binding site. Significantly, although most of the riboswitch architecture remained intact in the respective trajectories, the P3 stem was destabilized in the ligand-free simulations in a way that exposed the Shine–Dalgarno sequence. This work illustrates how destabilization of two major groove base triples can influence a nearby H-type pseudoknot and provides a mechanism for control of gene expression by a fold that is frequently found in bacterial riboswitches. 相似文献
96.
Audrey Damiens Anca-Elena Dascalu Mohammad Taghi Alebrahim Christophe Furman Emmanuelle Lipka Alina Ghinet Jean-Louis Hilbert Ali Siah Muriel Billamboz 《化学与生物多样性》2021,18(11):e2100224
As new environmentally friendly and effective antifungal agents are deeply needed, efficient ecofriendly strategies were designed to access two series of compounds inspired from natural γ-lactams. Designed compounds were fully characterized and evaluated as antifungal candidates against Zymoseptoria tritici, the main pathogen on wheat crops. The targeted derivatives were prepared from natural resources using green solvents, simple procedures, and limited purification steps. These bio-inspired compounds revealed as good candidates for further development of efficient crop protection products. Indeed, the HIT compounds exhibited IC50 around 1 μg/mL and were more active than the references tebuconazole and bixafen towards some multidrug-resistant strains. Two dozen of derivatives have been obtained for each series and allowed to establish early structure-activity relationships useful for the development of next generation of γ-lactam derivatives with improved efficacy. 相似文献
97.
Paulina Łyczko Anna Panek Ireneusz Ceremuga Alina Świzdor 《Microbial biotechnology》2021,14(5):2187-2198
Seventeen species of fungi belonging to thirteen genera were screened for the ability to carry out the transformation of 7-oxo-DHEA (7-oxo-dehydroepiandrosterone). Some strains expressed new patterns of catalytic activity towards the substrate, namely 16β-hydroxylation (Laetiporus sulphureus AM498), Baeyer–Villiger oxidation of ketone in D-ring to lactone (Fusicoccum amygdali AM258) and esterification of the 3β-hydroxy group (Spicaria divaricata AM423). The majority of examined strains were able to reduce the 17-oxo group of the substrate to form 3β,17β-dihydroxy-androst-5-en-7-one. The highest activity was reached with Armillaria mellea AM296 and Ascosphaera apis AM496 for which complete conversion of the starting material was achieved, and the resulting 17β-alcohol was the sole reaction product. Two strains of tested fungi were also capable of stereospecific reduction of the conjugated 7-keto group leading to 7β-hydroxy-DHEA (Inonotus radiatus AM70) or a mixture of 3β,7α,17β-trihydroxy-androst-5-ene and 3β,7β,17β-trihydroxy-androst-5-ene (Piptoporus betulinus AM39). The structures of new metabolites were confirmed by MS and NMR analysis. They were also examined for their cholinesterase inhibitory activity in an enzymatic-based assay in vitro test. 相似文献
98.
Y Zilberman A Ravid U A Liberman A Novogrodsky R Koren 《Biochimica et biophysica acta》1992,1134(3):297-302
Mouse medullary thymocytes have specific receptors for 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). The mitogenic stimulation of these cells by phytohemagglutinin in the presence or absence of the phorbol ester TPA is inhibited by 1,25(OH)2D3. The calcium ionophore A23187 did not reverse the inhibition by 1,25(OH)2D3 of phytohemagglutinin. Stimulation of thymocytes with either TPA or A23187 alone did not result in proliferation. Co-stimulation of the thymocytes with TPA and A23187 induces cell proliferation. 1,25(OH)2D3 markedly enhanced the TPA and A23187-induced cell proliferation even when added 4 h after the initiation of the culture. In contrast, DNA synthesis by thymocytes incubated for 4 h in the presence of TPA and A23187 and then cultured in medium containing 1,25(OH)2D3 but in the absence of both TPA and A23187, was inhibited by 1,25(OH)2D3. The extent of inhibition was comparable to the inhibition of lectin-induced stimulation by the hormone. Using monoclonal antibodies to neutralize IL-2 and block IL-2 receptors we showed that 1,25(OH)2D3 enhanced the IL-2-independent component of the A23187- and TPA-induced mitogenesis. In conclusion: (1) The nature and presence of the mitogenic signal determines whether 1,25(OH)2D3 enhances or inhibits thymocyte stimulation. (2) Both stimulatory and inhibitory actions of 1,25(OH)2D3 seem to take place at points distal to the initial increase in intracellular calcium or activation of protein kinase C. 相似文献
99.
Alina Asandei Sorana Iftemi Loredana Mereuta Irina Schiopu Tudor Luchian 《The Journal of membrane biology》2014,247(6):523-530
One of the prevailing paradigms regarding the onset of Alzheimer’s disease endows metal ions with key roles in certain steps of the amyloid-β (Aβ) peptide aggregation cascade, through peptide conformational changes induced by metal binding. Herein, we focused on the truncated, more soluble Aβ1–16 peptide fragment from the human Aβ1–40, and demonstrated the utility of a sensing element based on the α-hemolysin (α-HL) protein to examine and compare at single-molecule level the interactions between such peptides and various metals. By using the same approach, we quantified Cu2+ and Zn2+ binding affinities to the Aβ1–16 fragment, whereas the statistical analysis of blockages induced by a single Aβ1–16 peptide on the current flow through an open α-HL pore show that the metal propensity to interacting with the peptide and entailing conformational changes obey the following order: Cu2+ > Zn2+ > Fe3+ > Al3+. 相似文献
100.
Alina Blaszczyk Sylwia Matysiak Jozef Kula Katarzyna Szostakiewicz Zaneta Karkusiewicz 《Chirality》2020,32(7):998-1007
(R)-ricinoleic acid is the main component of castor oil from Ricinus communis L. Due to the presence of the hydroxyl group in homoallylic position and asymmetrically substituted carbon atom, it may undergo a number of chemical and biochemical transformations resulting in the products with some specific bioactivities. Conversion of (R)-ricinoleic acid into its (S)-enantiomer enables synthesis of both (R)- and (S)-ricinoleic acid derivatives and comparison of their biological activities. In the present research, (R)- and (S)-ricinoleic acid amides synthesized from methyl ricinoleates and ethanolamine or pyrrolidine as well as acetate derivatives of ethanolamine amides were studied to demonstrate their biological activities using HT29 cancer cells. Double staining of cells with fluorochromes (Hoechst 33258/propidium iodide) as well as 2,′7′-dichlorodihydrofluorescein (DCF) and comet assays were performed. Both the tested amides and acetates caused DNA damage and induced apoptotic and necrotic cell death. In the case of (R)- and (S)-enantiomers of one of the tested acetates, significant difference in the ability to induce DNA damage was observed, which showed the impact of the stereogenic center on the activities of these compounds. 相似文献