Preparation and Characterization of Paclitaxel Imprinted Silica Nanoparticles

2011 ◽  
Vol 399-401 ◽  
pp. 1894-1897
Author(s):  
Jian Hua Li ◽  
Zong Jian Zheng ◽  
Shao Ping Fu ◽  
Jing Bo Zhu

Highly selective molecularly imprinted layer-coated silica nanoparticles for paclitaxel were synthesized by molecular imprinting technique with a sol–gel process on the supporter of silica nanoparticles. The morphology of the obtained polymers was characterized by scanning electron microscopy (SEM). The binding properties of the imprinted polymers were evaluated through the equilibrium rebinding experiments. Scatchard analysis revealed that two classes of binding sites were formed in the imprinted polymers with equilibrium dissociation constants of 0.0509 g•L-1and 0.0094 g•L-1, respectively. Paclitaxel and its analogue were employed for selectivity tests. The results indicated that the imprinted polymers exhibited good selectivity and specificity toward paclitaxel.

2011 ◽  
Vol 239-242 ◽  
pp. 2423-2426
Author(s):  
Lin Min Zhu ◽  
Shao Ping Fu ◽  
Lin Ying Li ◽  
Jing Bo Zhu

Molecularly imprinted polymers (MIPs) were synthesized by precipitation polymerization using salvianolic acid A (Sal A), acrylamide (AA), ethylene glycol dimethacrylate (EGDMA) and acetonitrile as template molecule, functional monomer, cross-linker and solvent, respectively. The morphology of the obtained polymers was characterized by scanning electron microscopy (SEM). The effect of different polymerization conditions (solvent volume, solvent and template amount) on the size and shape of particles was investigated. The binding properties of the imprinted polymers were evaluated through the equilibrium rebinding experiments. Scatchard analysis revealed that two classes of binding sites were formed in the imprinted polymers with equilibrium dissociation constants of 0.33 μmol·mL-1and 0.07 μmol·mL-1, respectively. Besides Sal A, two structurally related compounds, protocatechuic aldehyde (Pra) and salvianolic acid B (Sal B), were employed for molecular selectivity tests. The results indicated that the imprinted polymers exhibited good selectivity and specificity toward Sal A.


2012 ◽  
Vol 197 ◽  
pp. 703-706
Author(s):  
Wei Shi ◽  
Jing Bo Zhu ◽  
Shao Ping Fu

Molecularly imprinted polymers of bisphenol A were synthesized with a sol-gel process on the supporter of silica nanospheres. The BPA-imprinted silica nanospheres were characterized by scanning electron microscope, dynamic adsorption, static adsorption tests and molecular selectivity tests. Scatchard analysis revealed that two classes of binding sites were formed in the imprinted polymers, the equilibrium association constant and the apparent maximum number of binding sites were estimated to be 0.20 μmol•ml-1 and 137.55 μmol•g-1, respectively. Bisphenol A and three analogues, tetrabromobisphenol A (TBBPA), bisphenol C (BPC) and nonylphenol (NP) were employed for selectivity tests. The results indicated that the imprinted polymers exhibited excellent selectivity and specificity toward bisphenol A.


1999 ◽  
Vol 84 (2) ◽  
pp. 805-810
Author(s):  
Dana L. Shkolny ◽  
Lenore K. Beitel ◽  
Jody Ginsberg ◽  
Gary Pekeles ◽  
Laura Arbour ◽  
...  

We have characterized two different mutations of the human androgen receptor (hAR) found in two unrelated subjects with androgen insensitivity syndrome (AIS): in one, the external genitalia were ambiguous (partial, PAIS); in the other, they were male, but small (mild, MAIS). Single base substitutions have been found in both individuals: E772A in the PAIS subject, and R871G in the MAIS patient. In COS-1 cells transfected with the E772A and R871G hARs, the apparent equilibrium dissociation constants (Kd) for mibolerone (MB) and methyltrienolone are normal. Nonetheless, the mutant hAR from the PAIS subject (E772A) has elevated nonequilibrium dissociation rate constants (kdiss) for both androgens. In contrast, the MAIS subject’s hAR (R871G) has kdiss values that are apparently normal for MB and methyltrienolone; in addition, the R871G hAR’s ability to bind MB resists thermal stress better than the hAR from the PAIS subject. The E772A and R871G hARs, therefore, confer the same pattern of discordant androgen-binding parameters in transfected COS-1 cells as observed previously in the subjects’ genital skin fibroblasts. This proves their pathogenicity and correlates with the relative severity of the clinical phenotype. In COS-1 cells transfected with an androgen-responsive reporter gene, trans-activation was 50% of normal in cells containing either mutant hAR. However, mutant hAR-MB binding is unstable during prolonged incubation with MB, whereas normal hAR-MB binding increases. Thus, normal equilibrium dissociation constants alone, as determined by Scatchard analysis, may not be indicative of normal hAR function. An increased kdiss despite a normal Kd for a given androgen suggests that it not only has increased egress from a mutant ligand-binding pocket, but also increased access to it. This hypothesis has certain implications in terms of the three-dimensional model of the ligand-binding domain of the nuclear receptor superfamily.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Angela M Phillips ◽  
Katherine R Lawrence ◽  
Alief Moulana ◽  
Thomas Dupic ◽  
Jeffrey Chang ◽  
...  

Over the past two decades, several broadly neutralizing antibodies (bnAbs) that confer protection against diverse influenza strains have been isolated. Structural and biochemical characterization of these bnAbs has provided molecular insight into how they bind distinct antigens. However, our understanding of the evolutionary pathways leading to bnAbs, and thus how best to elicit them, remains limited. Here, we measure equilibrium dissociation constants of combinatorially complete mutational libraries for two naturally isolated influenza bnAbs (CR9114, 16 heavy-chain mutations; CR6261, 11 heavy-chain mutations), reconstructing all possible evolutionary intermediates back to the unmutated germline sequences. We find that these two libraries exhibit strikingly different patterns of breadth: while many variants of CR6261 display moderate affinity to diverse antigens, those of CR9114 display appreciable affinity only in specific, nested combinations. By examining the extensive pairwise and higher-order epistasis between mutations, we find key sites with strong synergistic interactions that are highly similar across antigens for CR6261 and different for CR9114. Together, these features of the binding affinity landscapes strongly favor sequential acquisition of affinity to diverse antigens for CR9114, while the acquisition of breadth to more similar antigens for CR6261 is less constrained. These results, if generalizable to other bnAbs, may explain the molecular basis for the widespread observation that sequential exposure favors greater breadth, and such mechanistic insight will be essential for predicting and eliciting broadly protective immune responses.


2013 ◽  
Vol 641-642 ◽  
pp. 55-59 ◽  
Author(s):  
Yan Jie Bi ◽  
Wen Yan Li ◽  
Chen Yuan ◽  
Bin Song Wang

In this paper, molecularly imprinted polymers with high selectivity for nonylphenol (NP) were synthesized by sol-gel process using 4-vinylpyridine (4-Vpy) as functional monomer, ethyleneglycol dimethacrylate as crosslinker (EGDMA), azobisisobutyronitrile (AIBN) as initiator, NP as template molecules. The performance of imprinted material was evaluated by adsorption kinetic, adsorption isotherm and adsorption selectivity. The results indicated that this material had not only binding properties but also high selectivity to the template molecule, which had good application prospects in the selective enrichment and separation of NP for pretreatment and analysis of complex environmental samples.


2021 ◽  
Author(s):  
Angela M Phillips ◽  
Katherine R Lawrence ◽  
Alief Moulana ◽  
Thomas Dupic ◽  
Jeffrey Chang ◽  
...  

Over the past two decades, several broadly neutralizing antibodies (bnAbs) that confer protection against diverse influenza strains have been isolated. Structural and biochemical characterization of these bnAbs has provided molecular insight into how they bind distinct antigens. However, our understanding of the evolutionary pathways leading to bnAbs, and thus how best to elicit them, remains limited. Here, we measure equilibrium dissociation constants of combinatorially complete mutational libraries for two naturally isolated influenza bnAbs (CR-9114, 16 mutations; CR-6261, 11 mutations), reconstructing all possible intermediates back to the unmutated germline sequences. We find that these two libraries exhibit strikingly different patterns of breadth: while many variants of CR-6261 display moderate affinity to diverse antigens, those of CR-9114 display appreciable affinity only in specific, nested combinations. By examining the extensive pairwise and higher-order epistasis between mutations, we find key sites with strong synergistic interactions that are highly similar across antigens for CR-6261 and different for CR-9114. Together, these features of the binding affinity landscapes strongly favor sequential acquisition of affinity to diverse antigens for CR-9114, while the acquisition of breadth to more similar antigens for CR-6261 is less constrained. These results, if generalizable to other bnAbs, may explain the molecular basis for the widespread observation that sequential exposure favors greater breadth, and such mechanistic insight will be essential for predicting and eliciting broadly protective immune responses.


1985 ◽  
Vol 110 (1) ◽  
pp. 75-82 ◽  
Author(s):  
Dieter Ratge ◽  
Sabine Hansel-Bessey ◽  
Hermann Wisser

Abstract. We measured plasma catecholamines, α- and β-adrenoreceptor numbers and the accumulation of cyclic adenosine monophosphate (cAMP) in the unstimulated state and in response to 10 μmol/l (-) isoproterenol in blood cells from 29 euthyroid controls and from 18 patients with spontaneous hyperthyroidism. In the thyrotoxic patients plasma norepinephrine (1.14 ± 0.5 nmol/l) and epinephrine (0.3 ±0.14 nmol/l) were significantly decreased compared with plasma norepinephrine (1.87 ± 0.7 nmol) and epinephrine (0.41 ± 0.19 nmol/l) in the controls (P < 0.01 and P < 0.05, respectively) and the values obtained in subjects rendered euthyroid by antithyroid treatment (P < 0.001, respectively). α-adrenoceptor density in platelet membranes obtained from patients in the hyperthyroid state (114 ± 38 sites per cell) was significantly decreased when compared with controls (159 ± 48 sites per cell, P < 0.01) and the values from patients under effective antithyroid treatment (136 ± 35 sites per cell, P < 0.01). On the contrary, a significant increase in β-adrenoceptor density in mononuclear leucocyte (MNL) membranes was found in hyperthyroid patients (1751 ± 237 sites/cell) when compared with controls (1510 ± 351 sites/cell, P < 0.05) and the same patients following antithyroid treatment (1455 ± 260 sites/cell, P < 0.001). The equilibrium dissociation constants (KD) did not change in hyperthyroidism. Basal cAMP concentrations in MNL were higher in untreated thyrotoxicosis (45 ± 18 pmol/106 cells/10 min) than in patients in the euthyroid state (35 ± 9 pmol/106 cells/10 min, P < 0.05). Our data support the hypothesis that the balance of α- and β-adrenoceptors depends on the thyroid state. However, before the reputed catecholamine supersensitivity in hyperthyroid man can be accepted, the relationship between alterations in adrenoceptors and the biological responsiveness to catecholamines has to be demonstrated in different human tissues.


2004 ◽  
Vol 347 (1-3) ◽  
pp. 138-143 ◽  
Author(s):  
Hua-Kuo Chen ◽  
Hsin-Chin Hung ◽  
Thomas C.-K. Yang ◽  
Sea-Fue Wang
Keyword(s):  
Sol Gel ◽  

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