Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thermally responsive amphiphilic poly(N-isopropylacrylamide) (PNIPAm)-grafted-polyphosphazene (PNIPAm-g-PPP) was synthesized by stepwise cosubstitution of chlorine atoms on polymer backbones with amino-terminated NIPAm oligomers and ethyl glycinate (GlyEt). Polymer structure was confirmed by FT-IR, (1)H NMR, elemental analysis, and GPC. The thermosensitivity of PNIPAm-g-PPP aqueous solution was investigated by turbidity method. The lower critical solution temperature (LCST) of PNIPAm-g-PPP was observed to be approximately 30 degrees C in water, while it was 24 degrees C in 0.1M PBS (pH 7.4). Micellization behavior of PNIPAm-g-PPP in aqueous solution was characterized by fluorescence probe technique, TEM, and DLS. The critical micelle concentration (CMC), thus, determined was 0.0187 g/L. Both TEM and DLS measurement suggested that the diameter of micelles was approximately 190 nm at 20 degrees C. Diflunisal (DIF)-loaded micelles were prepared by dialysis method. In vitro release test at various temperatures was also performed to study the effect of temperature on the drug release profiles. It was demonstrated that DIF release from PNIPAm-g-PPP micelles was slower at the temperature of 37 degrees C than that at 4 degrees C.
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PMID:Thermally responsive polymeric micelles self-assembled by amphiphilic polyphosphazene with poly(N-isopropylacrylamide) and ethyl glycinate as side groups: polymer synthesis, characterization, and in vitro drug release study. 1634 95

In this work we evaluated the ability of 2,6-di-O-methyl-beta-cyclodextrin (DM-beta-Cyd) to include the anti-rhinovirus drug Disoxaril (WIN 51711), increasing its water solubility and stability. The complex, prepared by kneading method, was characterized in the solid state by differential scanning calorimetry and in aqueous solution using circular dichroism and NMR spectroscopy. The formation of 1:1 and 1:2 drug-Cyd complexes was hypothesized. Stability constants for both complexes were determined on the basis of an Ap-type phase solubility diagrams and evidenced a very high stability for the 1:1 complex. Thermodynamic parameters of the binding process showed the existence of classical hydrophobic interactions in the 1:1 complex with the formation of a less ordered system after complexation. An enthalpic contribution rather than an entropic one accompanied the association of the second Cyd molecule. DM-beta-Cyd was able to significantly increase water solubility of WIN 51711, from 0.000123 to 0.47142 mg/ml. Free drug shows a very low water stability, it is completely hydrolyzed after 36 h in PBS (pH 7.0), at 4 degrees C. In the presence of DM-beta-Cyd only a 10% of WIN 51711 was degraded, to the same conditions, after 12 days. DM-beta-Cyd increases the permeation of WIN 51711 across excised bovine nasal mucosa mounted on Franz cells, with respect to the free drug. Nevertheless, the permeation process had a lag time of 2 h so that the drug might assure its pharmacological activity on the outer surface of the mucosa. In vivo studies on rabbits evidenced that WIN 51711 is well tolerated, having no observable effect on the nasal mucosa following repeated administration.
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PMID:Physico-chemical characterization of disoxaril-dimethyl-beta-cyclodextrin inclusion complex and in vitro permeation studies. 1638 93

The nucleocapsid protein (NC) of HIV-1 exerts critical functions in viral genome replication and virus assembly. Since the recognition of target nucleic acids is required in the initial step of most NC-mediated processes, attempts were made to find small molecules capable of competing with this recognition. In particular, several Trp-rich hexapeptides were recently found to strongly bind RNA sequences targeted by NC. To further validate these peptides as potential anti-NC agents, we studied the ability of Ac-HKWPWW-NH2, taken as a representative, to interfere with the NC chaperone properties required during reverse transcription. Using NMR and steady-state and time-resolved fluorescence spectroscopy, we characterized the structure of Ac-HKWPWW-NH2 as well as its binding to viral sequences such as TAR and PBS involved in the two obligatory strand transfers of reverse transcription. Results show that Ac-HKWPWW-NH2 exhibits an almost symmetric cis-trans equilibrium at the level of the Pro residue where it is structured. The peptide binds both TAR and PBS sequences with low micromolar affinities. The cis-Pro and trans-Pro conformations of the peptide bind with comparable affinities to (-)PBS, mainly through stacking interactions between the Trp residues and the (-)PBS bases. Though all three Trp residues may contribute to the (-)PBS/Ac-HKWPWW-NH2 complex formation, Trp3 and Trp5 residues are the key residues in the complexes with the cis-Pro and trans-Pro conformations, respectively. Moreover, Ac-HKWPWW-NH2 stabilizes cTAR secondary structure and largely inhibits the NC-directed melting of cTAR. This further strengthens the interest of this peptide for deriving modified peptides capable of inhibiting NC and HIV-1 replication.
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PMID:A tryptophan-rich hexapeptide inhibits nucleic acid destabilization chaperoned by the HIV-1 nucleocapsid protein. 1686 72

A high-performance liquid chromatographic method has been developed to investigate the stability of solutions of flavone-8-acetic acid (LM975) during preparation and storage. LM975 (20 microg ml(-1) in PBS) was found to be completely stable for 10 days at 80 degrees C as long as light was rigorously excluded. The drug showed no significant adsorption to containers of different materials or to two filtration units tested. Drug degradation did occur however, on exposure to light. In normal laboratory light the t(0.95) (5% degraded) was 30.3 min, in intense natural light (laboratory window sill) the t(0.95) was 3.3 min and in intense artificial light (100 W bulb at 10 cm) the t(0.95) was 13.8 min. NMR and mass spectral analysis of the isolated degradation product implied the formation of the decarboxylated product, 8-methyl flavone. It is suggested that care be taken to exclude light during the preparation, storage and infusion of solutions of flavone-8-acetic acid.
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PMID:Stability of flavone-8-acetic acid (LM975) in aqueous solutions by high-performance liquid chromatography. 1686 56

Thermally sensitive micelles self-assembled from poly(N-isopropylacrylamide-co- N,N-dimethylacrylamide)-b-poly(d,l-lactide-co-glycolide)[P(NIPAAm-co-DMAAm)-b-PLGA] are fabricated and used as a carrier for the controlled delivery of paclitaxel. Paclitaxel is efficiently loaded into the micelles by a membrane dialysis method. The lower critical solution temperature (LCST) of the micelles is 39.0 degrees C in PBS. Encapsulation efficiency and loading level of paclitaxel are affected by the initial loading level of paclitaxel, fabrication temperature and polymer composition. The blank and paclitaxel-loaded micelles are characterized by particle size analysis (DLS), morphology (TEM and AFM) and paclitaxel distribution (NMR, DSC and WAXRD). The micelles are spherical in shape, having an average size less than 130 nm. Paclitaxel is molecularly distributed within the core of micelles. Sustained release of paclitaxel is achieved, which is much faster at a temperature above the LCST than at the normal body temperature (37 degrees C). Cytotoxicity of free paclitaxel and paclitaxel-loaded micelles against a human breast carcinoma cell line (MDA-MB-435S) is studied at different temperatures. The cytotoxicity of the paclitaxol-loaded micelles is greater as compared to free paclitaxel. Enhanced cytotoxicity is achieved by the paclitaxol-loaded micelles when the environmental temperature increases slightly above the LCST. Paclitaxel-loaded P(NIPAAm-co-DMAAm)-b-PLGA micelles may provide a good formulation for cancer therapy.
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PMID:Thermally sensitive micelles self-assembled from poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide)-b-poly(D,L-lactide-co-glycolide) for controlled delivery of paclitaxel. 1688 Sep 79

Dynamic light scattering, steady-state fluorescence, NMR diffusometry and cryo-TEM have been used to gain more insight into the aggregation behaviour of LPS from Escherichia coli O55:B5. Knowledge of this behaviour of the amphiphilic LPS molecule is in many cases of importance for the design of experiments and interpretation of results when using LPS in solution. The aim of this work was to study the aggregation and determine the aggregate size of E. coli O55:B5. The mean hydrodynamic radius of the LPS aggregates was determined by NMR diffusometry and dynamic light scattering to 14 and 26 nm, respectively. The cryo-TEM technique revealed predominantly spherical aggregates of 9-19 nm. We wish to report 10 microg/ml as the aggregation start for LPS E. coli O55:B5 in PBS buffer, pH 7.2. We suggest that the aggregation is a continuous process that starts at 10 microg/ml and proceeds up to 300 microg/ml.
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PMID:Aggregation behavior and size of lipopolysaccharide from Escherichia coli O55:B5. 1693 60

Dendrimers have been attracting growing attention because of their unique well-defined globular nanoscale architecture and numerous functional groups on the surface. Attachment of PEG to the dendrimer generates stealth dendrimers, which have promising structural advantages for drug delivery. In this study, synthetic methods were explored to deliver antiarrhythmic quinidine by stealth dendrimers. In particular, quinidine was covalently attached to anionic G2.5 and cationic G3.0 polyamidoamine (PAMAM) dendrimers via a glycine spacer, respectively. The resulting quinidine-PAMAM-PEG conjugates were characterized and confirmed by FT-IR and (1)H-NMR. In vitro hydrolysis was carried out in pH 7.4 PBS buffer at 37 degrees C to confirm the bioavailability of the conjugated quinidine.
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PMID:Stealth dendrimers for antiarrhythmic quinidine delivery. 1755 76

A new family of novel biodegradable poly(ether ester amide)s (PEEAs) consisting of three building blocks (L-phenylalanine, oligoethylene glycol, and aliphatic acid dichloride) were synthesized by solution polycondensation. Using N,N-dimethylacetamide as the solvent, these PEEA polymers were obtained with fairly good yields with reduced viscosity (eta(red)) ranging from 0.13 to 0.61 dL/g. The chemical structures of the PEEAs were confirmed by IR, NMR spectra, and elemental analysis. The PEEAs had Tg values lower than that of the saturated poly(ester amide)s (PEAs) of similar structures due to the incorporation of ether bonds in the backbones. An increase in the number of ether bonds in PEEA resulted in a lower Tg value. The solubility of the PEEA polymers in a wide range of common organic solvents was significantly improved when compared with unsaturated PEAs. The preliminary in vitro biodegradation behaviors of PEEA polymers were investigated in both pure PBS buffer and alpha-chymotrypsin solution of different concentrations. The polymers showed a significantly faster weight loss in an enzyme solution (alpha-chymotrypsin) but a very slow biodegradation rate in pure PBS buffer. The enzymatic hydrolysis rates of PEEAs (in terms of weight loss) were found to be much faster than those of saturated and unsaturated polyesteramides reported in previous studies. The zero-order-like biodegradation kinetics and molecular weight data also suggested surface erosion biodegradation mechanisms for these PEEAs.
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PMID:Synthesis, characterization, and biodegradation of novel poly(ether ester amide)s based on L-phenylalanine and oligoethylene glycol. 1767 2

Docetaxel (DCTX) and paclitaxel (PTX) are very potent anti-cancer drugs, but the currently marketed formulations, Taxotere and Taxol, respectively, are associated with vehicle-related toxicity. An attractive alternative to formulate these hydrophobic cytotoxic agents are polymeric micelles. In this study, the loading of taxanes into oligomeric micelles composed of mPEG750-b-oligo(epsilon-caprolactone)5 (mPEG750-b-OCL5) with a hydroxyl (OH), benzoyl (Bz) or naphthoyl (Np) end group was investigated. Next, the release characteristics and cytotoxicity of the loaded micelles were studied. MPEG750-b-OCL5 -OH micelles loaded with taxanes formed unstable particles with rapid leakage of the drug. In contrast, the presence of an aromatic end group (Bz or Np) resulted in the formation of small (10nm), almost monodisperse micelles with stable encapsulation of 10% (w/w) of PTX or DCTX. This was ascribed to a better compatibility between the micellar core and the drug as compared to the oligomers with the hydroxyl end group. 1H NMR studies showed that the micellar core was liquid, and that PTX was molecularly dissolved in the core. The in vitro stability was studied in PBS at 37 degrees C, which showed that leakage of PTX from 10% and 5% (w/w) loaded mPEG750-b-OCL5-Bz micelles started after 8 and 24h, respectively. The presence of albumin did not affect the stability, suggesting that the micelles are not destabilised and the drug was not extracted from the micellar core by this protein. The in vitro cytotoxic effect of the taxane-loaded micelles on C26 carcinoma cells was comparable to that of the commercial formulations, but the empty micelles were far less toxic than the Cremophor EL vehicle. The results show that mPEG-b-oligo(epsilon-caprolactone) micelles hold good promise for the formulation of taxanes.
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PMID:The effect of core composition in biodegradable oligomeric micelles as taxane formulations. 1794 56

A new lipopeptide with C12 fatty acid has been isolated from the cell broth of Bacillus subtilis HSO121 by chromatographic methods, which is believed to be the homologue of lipopeptides. The fatty acid portion was methylated and analyzed by GC/MS, ESI Q-TOF MS and 1H-NMR. The peptide portion, of which the amino acid composition was obtained by HPLC combined with a phenyl isothiocyanate (PITC) derivatization methods, was analyzed by ESI Q-TOF MS. Comparing the obtained results with surfactin C13 showed that the new lipopeptide has a peptide moiety similar to that of surfactin and the difference exists in the fatty acid portion, which is an iso-C12 beta-hydroxy fatty acid. The critical micelle concentration (CMC) of this new homologue is estimated to be 6.27 x 10(-5) mol/l in 10 mmol/l phosphate buffer solution (PBS, pH 8.0) at 30 degrees C, and the surface tension at CMC (gamma CMC) achieved is as little as 27.71 mN/m. The hemolytic activities of the C12-lipopeptide on 2% human erythrocytes showed a HC50 of 26.5 micromol/l.
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PMID:Isolation and characterization of a C12-lipopeptide produced by Bacillus subtilis HSO 121. 1826 35


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