Predictive tools for stabilization of therapeutic proteins

  • Voynov V
  • Chennamsetty N
  • Kayser V
 et al. 
  • 72

    Readers

    Mendeley users who have this article in their library.
  • 25

    Citations

    Citations of this article.

Abstract

Monoclonal antibodies represent the fastest growing class of pharmaceuticals. A major problem, however, is that the proteins are susceptible to aggregation at the high concentration commonly used during manufacturing and storage. Our recent publication describes a technology based on molecular simulations to identify aggregation-prone regions of proteins in silico. The technology, called spatial aggregation propensity (SAP), identifies hot-spots for aggregation based on the dynamic exposure of spatially-adjacent hydrophobic amino acids. Monoclonal antibodies (mAbs) in which patches with high-SAP scores are changed to patches with significantly reduced SAP scores via a single mutation are more stable than wild type, thus validating the SAP method for mapping aggregation-prone regions on proteins. We propose that the SAP technology will be useful for protein stabilization, and as a screening tool to bridge discovery and development of protein-based therapeutics by a rational assessment of the developability of candidate protein drugs.

Author-supplied keywords

  • Aggregation
  • Enhanced protein stability
  • Genetic engineering
  • Molecular simulations
  • Therapeutic antibodies

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Vladimir Voynov

  • Naresh Chennamsetty

  • Veysel Kayser

  • Bernhard Helk

  • Bernhardt L. Trout

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free