Pubfacts - Scientific Publication Data
  • Categories
  • |
  • Journals
  • |
  • Authors
  • Login
  • Categories
  • Journals

Search Our Scientific Publications & Authors

Publications
  • Publications
  • Authors
find publications by category +
Translate page:

Structure and function of purified monoclonal antibody dimers induced by different stress conditions.

Authors:
Rajsekhar Paul Alexandra Graff-Meyer Henning Stahlberg Matthias E Lauer Arne C Rufer Hermann Beck Alexandre Briguet Volker Schnaible Thomas Buckel Sabine Boeckle

Pharm Res 2012 Aug 5;29(8):2047-59. Epub 2012 Apr 5.

Pharma Technical Development Europe (Biologics) Analytics, F. Hoffmann-La Roche Ltd., 4070, Basel, Switzerland.

Purpose: To investigate structure and function of different monoclonal antibody (MAb) dimers.

Methods: MAb dimers were induced by process-related, low pH and UV light stress. Dimers were isolated and purified by chromatography and extensively characterized by biochemical, structural and functional methods.

Results: Highly purified dimer forms were obtained which enabled detailed characterization. Dimers induced by process stress were associated by a single non-covalent interaction site between two Fab domains in a characteristic "bone-like" structure observed in Transmission Electron Microscopy (TEM). These dimers showed reduced potency and antigen binding affinity. Low pH stress generated more stable but also non-covalently associated dimers without chemical alterations in a typical "closed" conformation according to TEM. These dimer species were more compact and more hydrophobic as dimers induced by process stress. They showed bioactivity and antigen binding affinity similar to the native monomer. Light-induced dimers, exhibiting various different conformations, were the most stable dimers with various chemical modifications leading to a broad range in size, charge and hydrophobicity. These dimers fully lost bioactivity and antigen binding affinity.

Conclusion: The use of highly purified MAb dimers and a panel of characterizations methods enabled to obtain a clear picture about molecular architecture and function of dimers.

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11095-012-0732-6DOI Listing
August 2012

Publication Analysis

Top Keywords

dimers induced
16
dimers
12
antigen binding
12
highly purified
8
bioactivity antigen
8
induced process
8
process stress
8
mab dimers
8
binding affinity
8
dimers chemical
8
structure function
8
monoclonal antibody
8
stress
5
enabled detailed
4
native monomer
4
site fab
4
monomer light-induced
4
interaction site
4
fab domains
4
domains characteristic
4

Similar Publications

Sex Differences in Photoprotective Responses to 1,25-Dihydroxyvitamin D3 in Mice Are Modulated by the Estrogen Receptor-β.

Authors:
Wannit Tongkao-On Chen Yang Bianca Y McCarthy Warusavithana G Manori De Silva Mark S Rybchyn Clare Gordon-Thomson Katie M Dixon Gary M Halliday Vivienne E Reeve Rebecca S Mason

Int J Mol Sci 2021 Feb 16;22(4). Epub 2021 Feb 16.

Department of Physiology, University of Sydney, Sydney, NSW 2006, Australia.

Susceptibility to photoimmune suppression and photocarcinogenesis is greater in male than in female humans and mice and is exacerbated in female estrogen receptor-beta knockout (ER-β-/-) mice. We previously reported that the active vitamin D hormone, 1,25-dihydroxyvitamin D3 (1,25(OH)2D), applied topically protects against the ultraviolet radiation (UV) induction of cutaneous cyclobutane pyrimidine dimers (CPDs) and the suppression of contact hypersensitivity (CHS) in female mice. Here, we compare these responses in female versus male Skh:hr1 mice, in ER-β-/-/-- versus wild-type C57BL/6 mice, and in female ER-blockaded Skh:hr1 mice. Read More

View Article and Full-Text PDF
February 2021
Similar Publications

Interleukin 17 Promotes Expression of Alarmins S100A8 and S100A9 During the Inflammatory Response of Keratinocytes.

Authors:
Carolin Christmann Stefanie Zenker Leonie Martens Janina Hübner Karin Loser Thomas Vogl Johannes Roth

Front Immunol 2020 12;11:599947. Epub 2021 Feb 12.

Institute of Immunology, University of Muenster, Muenster, Germany.

Psoriasis is one of the most common immune-mediated inflammatory skin diseases. Expression and secretion of two pro-inflammatory molecules of the S100-alarmin family, S100A8 and S100A9, in keratinocytes is a hallmark of psoriasis, which is also characterized by an altered differentiation of keratinocytes. Dimers of S100A8/S100A9 (calprotectin) bind to Toll-like receptor 4 and induce an inflammatory response in target cells. Read More

View Article and Full-Text PDF
February 2021
Similar Publications

Time-Dependent Molecular Rearrangement of [Au(-adeninate)(PTA)] in Aqueous Solution and Aggregation-Induced Emission in a Hydrogel Matrix.

Authors:
Daniel Blasco José M López-de-Luzuriaga Miguel Monge M Elena Olmos David Pascual María Rodríguez-Castillo

Inorg Chem 2021 Feb 26. Epub 2021 Feb 26.

Departamento de Química, Universidad de La Rioja, Centro de Investigación en Síntesis Química (CISQ), Complejo Científico Tecnológico, 26004 Logroño, Spain.

An in-depth study of the molecular rearrangement of the complex [Au(-adeninate)(PTA)] (), promoted in aqueous solution, is presented. This complex, which has been previously described as forming dimers in its crystalline form, is also demonstrated as being able to assemble into an infinite Au···Au chain polymer. The structural motifs are tentatively related to the dramatic modification of the photoemissive properties of in water solution at long times, with the aid of UV-vis and photoluminescence measurements, PGSE-NMR, and theoretical calculations. Read More

View Article and Full-Text PDF
February 2021
Similar Publications

Structure-function relationship of the platelet glycoprotein VI (GPVI) receptor: does it matter if it is a dimer or monomer?

Authors:
Joanne C Clark Foteini-Nafsika Damaskinaki Yam Fung Hilaire Cheung Alexandre Slater Steve P Watson

Platelets 2021 Feb 26:1-8. Epub 2021 Feb 26.

Institute of Cardiovascular Sciences, Level 1 IBR, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.

GPVI is a critical signaling receptor responsible for collagen-induced platelet activation and a promising anti-thrombotic target in conditions such as coronary artery thrombosis, ischemic stroke, and atherothrombosis. This is due to the ability to block GPVI while having minimal effects on hemostasis, making it a more attractive target over current dual-antiplatelet therapy (DAPT) with acetyl salicylic acid and P2Y inhibitors where bleeding can be a problem. Our current understanding of how the structure of GPVI relates to function is inadequate and recent studies contradict each other. Read More

View Article and Full-Text PDF
February 2021
Similar Publications

Pharmacologic targeting of plasma cell endoplasmic reticulum proteostasis to reduce amyloidogenic light chain secretion.

Authors:
Bibiana Rius Jaleh S Mesgarzadeh Isabelle C Romine Ryan J Paxman Jeffery W Kelly R Luke Wiseman

Blood Adv 2021 Feb;5(4):1037-1049

Department of Molecular Medicine.

Light chain (LC) amyloidosis (AL) involves the toxic aggregation of amyloidogenic immunoglobulin LCs secreted from a clonal expansion of diseased plasma cells. Current AL treatments use chemotherapeutics to ablate the AL plasma cell population. However, no treatments are available that directly reduce the toxic LC aggregation involved in AL pathogenesis. Read More

View Article and Full-Text PDF
February 2021
Similar Publications
© 2021 PubFacts.
  • About PubFacts
  • Privacy Policy
  • Sitemap