Repository logo

Infoscience

  • English
  • French
Log In
Logo EPFL, École polytechnique fédérale de Lausanne

Infoscience

  • English
  • French
Log In
  1. Home
  2. Academic and Research Output
  3. Journal articles
  4. Structure and Function of Purified Monoclonal Antibody Dimers Induced by Different Stress Conditions
 
research article

Structure and Function of Purified Monoclonal Antibody Dimers Induced by Different Stress Conditions

Paul, Rajsekhar
•
Graff-Meyer, Alexandra
•
Stahlberg, Henning  orcid-logo
Show more
April 5, 2012
Pharmaceutical Research

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

  • Details
  • Metrics
Type
research article
DOI
10.1007/s11095-012-0732-6
Author(s)
Paul, Rajsekhar
Graff-Meyer, Alexandra
Stahlberg, Henning  orcid-logo
Lauer, Matthias E.
Rufer, Arne C.
Beck, Hermann
Briguet, Alexandre
Schnaible, Volker
Buckel, Thomas
Boeckle, Sabine
Date Issued

2012-04-05

Publisher

Springer Nature

Published in
Pharmaceutical Research
Volume

29

Issue

8

Start page

2047

End page

2059

Editorial or Peer reviewed

REVIEWED

Written at

OTHER

EPFL units
LBEM  
Available on Infoscience
February 13, 2020
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/165414
Logo EPFL, École polytechnique fédérale de Lausanne
  • Contact
  • infoscience@epfl.ch

  • Follow us on Facebook
  • Follow us on Instagram
  • Follow us on LinkedIn
  • Follow us on X
  • Follow us on Youtube
AccessibilityLegal noticePrivacy policyCookie settingsEnd User AgreementGet helpFeedback

Infoscience is a service managed and provided by the Library and IT Services of EPFL. © EPFL, tous droits réservés