Abstract：
:To determine how structural changes in antibodies are connected with aggregation, the structural areas of an antibody prone to and/or impacted by aggregation must be identified. In this work, the higher-order structure and biophysical properties of two different monoclonal antibody (mAb) monomers were compared with their simplest aggregated form, that is, dimers that naturally occurred during normal production and storage conditions. A combination of hydrogen/deuterium exchange mass spectrometry and other biophysical measurements was used to make the comparison. The results show that the dimerization process for one of the mAb monomers (mAb1) displayed no differences in its deuterium uptake between monomer and dimer forms. However, the other mAb monomer (mAb2) showed subtle changes in hydrogen/deuterium exchange as compared with its dimer form. In this case, differences observed were located in specific functional regions of the CH 2 domain and the hinge region between CH 1 and CH 2 domains. The importance and the implications of these changes on the antibody structure and mechanism of aggregation are discussed.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Iacob RE,Bou-Assaf GM,Makowski L,Engen JR,Berkowitz SA,Houde Ddoi
10.1002/jps.23754subject
Has Abstractpub_date
2013-12-01 00:00:00pages
4315-29issue
12eissn
0022-3549issn
1520-6017pii
S0022-3549(15)30810-8journal_volume
102pub_type
杂志文章abstract：:Despite being a major breakthrough in multiple myeloma therapy, carfilzomib (CFZ, a second-generation proteasome inhibitor drug) has been largely ineffective against solid cancer, possibly due to its pharmacokinetic drawbacks including metabolic instability. Recently, quinic acid (QA, a low-affinity ligand of selectin...
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journal_title：Journal of pharmaceutical sciences
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journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600740319
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journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600790503
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abstract：:Ion cluster technique in conjunction with gas chromatography-mass spectrometry (GC-MS) was used for the identification and quantitation of major metabolites of cocaine (1a) in rat and humans. In a typical experiment, a female rat weighing 250 gm was intraperitoneally administered a 20-mg/kg mixture of 1a, NCD3-cocaine...
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journal_title：Journal of pharmaceutical sciences
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更新日期：1976-11-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
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更新日期：1982-11-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
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更新日期：2017-10-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600681119
更新日期：1979-11-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600670643
更新日期：1978-06-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.21492
更新日期：2009-03-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
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doi：10.1016/j.xphs.2020.08.021
更新日期：2020-12-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
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doi：10.1021/js9504189
更新日期：1996-04-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600710710
更新日期：1982-07-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600730911
更新日期：1984-09-01 00:00:00
abstract：:Corneal penetration studies were conducted in unanesthetized albino rabbits using various organic compounds representing both polar and nonpolar species. Very low molecular weight compounds demonstrate rapid uptake into the aqueous humor despite the lipid-like barrier imposed by the corneal epithelium. Evidence that t...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600770103
更新日期：1988-01-01 00:00:00
abstract：:This edition of the Journal of Pharmaceutical Sciences is dedicated to the wonderful career of Per Artursson from the Uppsala University. My Commentary focusses on Per's major contributions to the Caco-2 cell literature over the past 30 years. Two especially influential papers have been cited more than 1000 times out ...
journal_title：Journal of pharmaceutical sciences
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doi：10.1016/j.xphs.2020.08.016
更新日期：2021-01-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
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更新日期：2008-12-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600771011
更新日期：1988-10-01 00:00:00
abstract：:A thermally responsive nanogel was developed through the radical polymerization based on chitosan (CTS) and N-isopropylacrylamide (NIPAAm) with acrylamide (AAm) blended to explore the possibility of increasing the volume phase transition temperature (VPTT). The thermally sensitive features of resultant nanogels were s...
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更新日期：2014-07-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23221
更新日期：2012-08-01 00:00:00
abstract：:The crystal structures of the analgesic compounds anhydrous naloxone and naltrexone hydrochloride were determined ab initio from high resolution laboratory X-ray powder diffraction data. Both compounds crystallize in the orthorhombic space group P2(1)2(1)2(1) with lattice parameters of a = 14.6588(10) A, b = 17.4363(9...
journal_title：Journal of pharmaceutical sciences
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更新日期：2007-12-01 00:00:00
abstract：:A wide variety of computational models covering statistical, mechanistic, and machine learning (locked and adaptive) methods are explored for use in biopharmaceutical manufacturing. Limited discussion exists on how to establish the credibility of a computational model for application in biopharmaceutical manufacturing...
journal_title：Journal of pharmaceutical sciences
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更新日期：2021-01-22 00:00:00
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journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600650308
更新日期：1976-03-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600740713
更新日期：1985-07-01 00:00:00
abstract：:The recently introduced four-parameter extended Hansen approach was used to study the solubility of p-hydroxybenzoic acid and methyl p-hydroxybenzoate in 32 and 35 individual solvents, respectively. The results are compared with those for benzoic acid in 40 solvents. Seventeen of the thirty-two or 53% of the calculate...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600730211
更新日期：1984-02-01 00:00:00
