Biophysical characterization of insoluble aggregates of a multi-domain protein: an insight into the role of the various domains.


:Insoluble (visible) aggregates of a homodimer fusion glycoprotein, consisting of the first extracellular domain of a human protein, fused to the hinge, C(H)2, and C(H)3 domains of a human immunoglobulin G(1) (IgG(1)), were observed during early formulation development. The soluble fraction of the fusion protein was compared to the visible aggregates by various biophysical techniques such as intrinsic and ANS fluorescence emission, reducing and nonreducing SDS-PAGE, equilibrium folding and refolding experiments in urea and guanidine hydrochloride in the absence and presence of mercaptoethanol. Significant differences were observed between the visible aggregates and the supernatant. Partial unfolding of the aggregated molecules was detected by intrinsic and ANS fluorescence. Using urea and guanidine hydrochloride unfolding/solubilization and refolding curves, it was possible to extrapolate that (i) the aggregates were not covalently linked but tightly associated, (ii) the fused domains of the protein were unfolded but not involved in the aggregation process, (iii) the C(H)2 domains were native-like, and (iv) the C(H)3 domains were involved in the aggregation process.


J Pharm Sci


Souillac PO




Has Abstract


2005-09-01 00:00:00














  • The use of 13C labeling to enhance the sensitivity of 13C solid-state CPMAS NMR to study polymorphism in low dose solid formulations.

    abstract::(13)C labeling was used to enhance the sensitivity of (13)C solid-state NMR to study the effect of tabletting on the polymorphism of a steroidal drug. The steroidal drug Org OD 14 was (13)C labeled and formulated into tablets containing only 0.5-2.5% active ingredient. The tablets were subsequently studied by solid-st...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Booy KJ,Wiegerinck P,Vader J,Kaspersen F,Lambregts D,Vromans H,Kellenbach E

    更新日期:2005-02-01 00:00:00

  • Quantitative flash-methylation analysis of phenobarbital.

    abstract::In phenobarbital measurement by GLC with the flash-methylation technique, using trimethylanilinium hydroxide as a methylating reagent, a small amount of water decomposed phenobarbital and interfered with the quantitative analysis. Thus, both the sample and the methylating reagent must be sufficiently dehydrated to att...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Kurata K,Takeuchi M,Yoshida K

    更新日期:1979-09-01 00:00:00

  • A hot-melt extruded intravaginal ring for the sustained delivery of the antiretroviral microbicide UC781.

    abstract::Microbicide intravaginal rings (IVRs) are a promising woman-controlled strategy for preventing sexual transmission of human immunodeficiency virus (HIV). An IVR was prepared and developed from polyether urethane (PU) elastomers for the sustained delivery of UC781, a highly potent nonnucleoside reverse transcriptase in...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Clark MR,Johnson TJ,McCabe RT,Clark JT,Tuitupou A,Elgendy H,Friend DR,Kiser PF

    更新日期:2012-02-01 00:00:00

  • Kinetics of chlorambucil hydrolysis using high-pressure liquid chromatography.

    abstract::A stability-specific high-pressure liquid chromatographic (HPLC) method was developed to assay intact chlorambucil (I) in the presence of its hydrolytic decomposition products. The HPLC method was used to follow the degradation kinetics of I over pH 1.0-10.0 in the presence of various buffers with and without added ch...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Chatterji DC,Yeager RL,Gallelli JF

    更新日期:1982-01-01 00:00:00

  • Preformulation and pharmacokinetic studies on antalarmin: a novel stress inhibitor.

    abstract::The preformulation, solubilization and pharmacokinetic evaluation of antalarmin, a stress inhibitor, have been conducted. Antalarmin has a poor water solubility of less than 1 microg/mL and is weakly basic with an experimentally determined pK(a) of 5.0. Multiple solubilization approaches including pH-control either al...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Sanghvi R,Mogalian E,Machatha SG,Narazaki R,Karlage KL,Jain P,Tabibi SE,Glaze E,Myrdal PB,Yalkowsky SH

    更新日期:2009-01-01 00:00:00

  • Cholesterol-Targeted Anticancer and Apoptotic Effects of Anionic and Polycationic Amphiphilic Cyclodextrin Nanoparticles.

    abstract::Amphiphilic cyclodextrins (CDs) are biocompatible derivatives of natural CDs and are able to form nanoparticles or polyplexes spontaneously. In this study, nanoparticles prepared from nonionic (6OCaproβCD) or cationic amphiphilic CD (PC βCDC6) were used comparatively to develop nanoparticles intended for breast cancer...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Varan G,Öncül S,Ercan A,Benito JM,Ortiz Mellet C,Bilensoy E

    更新日期:2016-10-01 00:00:00

  • Physico-chemical and technological properties of sodium naproxen granules prepared in a high-shear mixer-granulator.

    abstract::In the present work, authors produced tablets of anhydrous sodium naproxen by wet granulation using a high-shear mixer-granulator. Drug hydrated to the tetrahydrated form, as observed by X-ray powder diffractometry. After wet granulation, authors then performed two different drying procedures, obtaining granules of di...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Di Martino P,Malaj L,Censi R,Martelli S

    更新日期:2008-12-01 00:00:00

  • Preparation of inhalable salbutamol sulphate using reactive high gravity controlled precipitation.

    abstract::Reactive high gravity controlled precipitation (HGCP) was carried out to produce salbutamol sulphate (SS) particles suitable for inhalation. Aqueous solutions of free salbutamol base and sulphuric acid were mixed intensely inside a HGCP reactor to form the particles. Spray drying was employed to obtain dry powders. Ph...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Hu T,Chiou H,Chan HK,Chen JF,Yun J

    更新日期:2008-02-01 00:00:00

  • Effect of inorganic additives on solutions of nonionic surfactants V: Emulsion stability.

    abstract::Electrolytes often break emulsions to which they were added as active ingredients, adjuvants, or impurities. The stability of oil-in-water emulsions containing octoxynol 9 NF as the emulsifier and various added electrolytes was investigated by measuring droplet size, turbidity, and oil separation on storage at various...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Schott H,Royce AE

    更新日期:1983-12-01 00:00:00

  • Stereospecific assay and stereospecific disposition of racemic carprofen in rats.

    abstract::A procedure was developed for the separation and selective quantitative determination of the (S)(+)- and (R)(-)-enantiomers of the racemic anti-inflammatory drug carprofen as their diastereomeric l-(-)-alpha-methylbenzylamides. These derivatives are obtained in equivalent yields by reacint purified 14C-carprofen from ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Kemmerer JM,Rubio FA,McClain RM,Koechlin BA

    更新日期:1979-10-01 00:00:00

  • Influence of asymmetric donor-receiver ion concentration upon transscleral iontophoretic transport.

    abstract::Recent in vitro and in vivo studies have suggested transscleral iontophoresis as a means for non-invasive drug delivery to the eye. However, there remains a lack of information of the iontophoretic transport behavior of the sclera. The objective of the present study was to investigate the effects of permeant concentra...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Li SK,Zhang Y,Zhu H,Higuchi WI,White HS

    更新日期:2005-04-01 00:00:00

  • Easy and practical utilization of CONSAM for simulation, analysis, and optimization of complex dosing regimens.

    abstract::Complex dosing regimens simulated in the literature using a universal dosing regimen were calculated with a general dosing program developed using the program CONSAM. The program provides a rapid method of calculating nonuniform dosing regimens for up to n = 3 compartments for any linear model. Subject data can also b...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Jackson AJ,Zech LA

    更新日期:1991-04-01 00:00:00

  • Enzyme immunoassay for captopril.

    abstract::A simple enzyme immunoassay for the determination of captopril was developed. A specific antibody for captopril was produced in rabbits that were immunized with a hapten-bovine immunoglobulin G conjugate, which was prepared by using 4-(maleimidomethyl)cyclohexane carboxylic acid as a spacer group. The limit of detecti...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Kinoshita H,Nakamaru R,Tanaka S,Tohira Y,Sawada M

    更新日期:1986-07-01 00:00:00

  • Role of Solvent Selection on Crystal Habit of 5-Aminosalicylic Acid-Combined Experimental and Computational Approach.

    abstract::Many active pharmaceutical ingredients exhibit a needle-like (acicular) crystal habit, which can significantly complicate their downstream processing. In this study, the acicular crystal habit of a model active pharmaceutical ingredient, 5-aminosalicylic acid (5-ASA), was modified by addition of selected organic solve...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Pudasaini N,Parker CR,Hagen SU,Bond AD,Rantanen J

    更新日期:2018-04-01 00:00:00

  • 3D Printing of Solid Oral Dosage Forms: Numerous Challenges With Unique Opportunities.

    abstract::Since the FDA approval of Spritam, there has been a growing interest in the application of 3D printing in pharmaceutical science. 3D printing is a method of manufacturing involving the layer-by-layer deposition of materials to create a final product according to a digital model. There are various techniques used to ac...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章,评审


    authors: Okafor-Muo OL,Hassanin H,Kayyali R,ElShaer A

    更新日期:2020-12-01 00:00:00

  • Steady-state pharmacokinetics of haloperidol and reduced haloperidol in schizophrenic patients: analysis of factors determining their concentrations in hair.

    abstract::Profiles of the steady-state concentrations of haloperidol (HL) and its major metabolite, reduced haloperidol (RHL), in plasma versus time were determined in 10 Japanese patients whose schizophrenic symptoms were clinically controlled by fixed, oral maintenance doses (4-30 mg/day, three times a day) for greater than 4...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Uematsu T,Matsuno H,Sato H,Hirayama H,Hasegawa K,Nakashima M

    更新日期:1992-10-01 00:00:00

  • Synthesis and antibacterial evaluation of 2-(substituted phenylureido)-4-thiocyanatobenzothiazoles.

    abstract::The synthesis and antibacterial evaluation of a number of 2-(substituted phenylureido)-4-thiocyanatobenzothiazoles are described. The more active compounds against the test organisms in vitro generally were those substituted with halogens on the phenyl and benzothiazole rings. ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Alaimo RJ,Pelosi SS,Freedman R

    更新日期:1978-02-01 00:00:00

  • Effect of symmetrical tetraalkylammonium salts on cloud point on nonionic surfactants.

    abstract::The salting in and salting out of the nonionic surfactant octoxynol NF by halides of ammonium and the four lowest symmetrical tetraalkylammonium cations were investigated by measuring their effect on the cloud point at various salt concentrations. The chloride anion tended to salt the surfactant out, lowering its clou...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Schott H,Han SK

    更新日期:1977-02-01 00:00:00

  • Pharmacokinetics and metabolism of bisoprolol enantiomers in humans.

    abstract::The plasma concentrations and urinary excretions of bisoprolol enantiomers in four Japanese male healthy volunteers after a single oral administration of 20 mg of racemic bisoprolol were evaluated. The AUC(infinity) and elimination half-life of (S)-(-)-bisoprolol were slightly larger than those of (R)-(+)-bisoprolol i...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 临床试验,杂志文章


    authors: Horikiri Y,Suzuki T,Mizobe M

    更新日期:1998-03-01 00:00:00

  • Quantitative structure-activity relationships and dipole moments of anticonvulsants and CNS depressants.

    abstract::The anticonvulsant and CNS-depressant activities of 16 commercially available antiepileptics were subjected to regression analysis. For the maximal electroshock seizure test and pentylenetetrazol seizure threshold test, good correlations were obtained only after diazepam, clonazepam, and carbamazepam were deleted; for...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Lien EJ,Liao RC,Shinouda HG

    更新日期:1979-04-01 00:00:00

  • Structure Determination and Characterization of a Family of Primary Alcohol Solvates.

    abstract::We report the preparation and structural characterization of a family of primary alcohol solvates of a small-molecule hydrochloride salt. The structures of the solvates are probed by powder and single crystal X-ray diffraction, and the compounds were additionally characterized by polarized light microscopy, thermograv...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Vasudevan KV,Peterson ML

    更新日期:2018-06-01 00:00:00

  • Pharmacokinetics of dopamine-2 agonists in rats and dogs.

    abstract::The absorption, protein binding, blood-to-plasma ratio, renal excretion, and pharmacokinetics of the dopamine-2 agonists (D2-agonists) 4-(2-di-n-propylaminoethyl)-7-hydroxy-2-(3H)-indolone (1), N-(2'-hydroxy-5'-[N,N-di-n-propylaminoethylphenyl])methanesulfonamide (2), and 4-(2-di-n-propylaminoethyl)-2-(3H)-indolone (3...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Swagzdis JE,Wittendorf RW,DeMarinis RM,Mico BA

    更新日期:1986-10-01 00:00:00

  • Drug delivery trends in clinical trials and translational medicine: evaluation of pharmacokinetic properties in special populations.

    abstract::In spite of the recent advances in technology to optimize the absorption, distribution, metabolism and elimination (ADME) properties of new and promising medicinal products to reduce clinical failures, the investigation of drug disposition in the pediatric and elderly populations continues to be under evaluated. With ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章,评审


    authors: Chien JY,Ho RJ

    更新日期:2011-01-01 00:00:00

  • Drying-induced variations in physico-chemical properties of amorphous pharmaceuticals and their impact on stability (I): stability of a monoclonal antibody.

    abstract::The present study was conducted to investigate the impact of drying method and formulation on the storage stability of IgG1. Formulations of IgG1 with varying levels of sucrose with and without surfactant were dried by different methods, namely freeze drying, spray drying, and foam drying. Dried powders were character...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Abdul-Fattah AM,Truong-Le V,Yee L,Nguyen L,Kalonia DS,Cicerone MT,Pikal MJ

    更新日期:2007-08-01 00:00:00

  • Antitumor efficacy of taxane liposomes on a human ovarian tumor xenograft in nude athymic mice.

    abstract::Taxanes such as paclitaxel (Taxol) and docetaxel (Taxotere) are promising agents for use against ovarian cancer and other malignancies. Recently, SB-T-1011, a semisynthetic taxane, has been prepared from 14-hydroxy-10-deacetylbaccatin III. SB-T-1011 shows similar or greater in vitro cytostatic activity than paclitaxel...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Sharma A,Straubinger RM,Ojima I,Bernacki RJ

    更新日期:1995-12-01 00:00:00

  • Transformation of 2,2'-anhydro-1-beta-D-arabinofuranosylcytosine induced by hydrogen peroxide.

    abstract::2,2'-Anhydro-1-beta-D-arabinofuranosylcytosine (I) is a more potent and less toxic antineoplastic agent than is cytarabine (1-beta-D-arabinofuranosylcytosine) (II). The anhydronucleoside (I) was found to be readily transformed by hydrogen peroxide into 2,2'-anhydro-5-hydroxy-1-beta-D-arabinofuranosylcytosine (III) by ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Kikugawa K

    更新日期:1975-03-01 00:00:00

  • Colorimetric acetaminophen determination in pharmaceutical formulations.

    abstract::Different approaches for the colorimetric determination of acetaminophen, based on its coupling with diazotized o-nitroaniline, are described. Copper(II) chelation with the coupled compound makes the method highly selective. Sensitivity is increased when the acetaminophen assay is carried out indirectly through the de...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Belal S,Elsayed MA,El-Waliely A,Abdine H

    更新日期:1979-06-01 00:00:00

  • Physicochemical and structural characterization of quercetin-beta-cyclodextrin complexes.

    abstract::Quercetin is a bioactive flavonoid widely used as a health supplement. Being sparingly soluble and chemically unstable in aqueous intestinal fluids, quercetin is poorly absorbed orally. This study aimed to investigate the effects of three beta-cyclodextrins, namely, unsubstituted beta-cyclodextrin (beta-CD), hydroxypr...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Zheng Y,Haworth IS,Zuo Z,Chow MS,Chow AH

    更新日期:2005-05-01 00:00:00

  • Stability of tetrahydrocannabinols II.

    abstract::The biphasic degradation of delta9-tetrahydrocannabinol (I), as monitored by flame-ionization GLC, produced delta8-tetrahydrocannabinol (II), cannabidiol (X), 9-hydroxyhexahydrocannabinol (VI), 9,10-dihydro-9-hydroxyisocannabidiol (VI), and and 6,12-dihydro-6-hydroxycannabidiol (VIII) in acidic solutions. Further iden...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Garrett ER,Gouyette AJ,Roseboom H

    更新日期:1978-01-01 00:00:00

  • Isolation of cannabisativine, an alkaloid, from Cannabis sativa L. root.

    abstract::An ethanol extract of the root of a Mexican variant of Cannabis sativa L.(marijuana) afforded, after partitioning and chromatography, the new spermidine alkaloid cannabisativine. ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Turner CE,Hsu MH,Knapp JE,Schiff PL Jr,Slatkin DJ

    更新日期:1976-07-01 00:00:00