Advancing therapeutic protein discovery and development through comprehensive computational and biophysical characterization

Research output: Contribution to journalArticlepeer-review

  • External authors:
  • Lorenzo Gentiluomo
  • Hristo L. Svilenov
  • Dillen Augustijn
  • Inas El Bialy
  • Maria Laura Greco
  • Alina Kulakova
  • Sowmya Indrakumar
  • Sujata Mahapatra
  • Marcello Martinez Morales
  • Christin Pohl
  • Aisling Roche
  • Andreas Tosstorff
  • Allan Norgaard
  • Tarik A. Khan
  • Gunther H. J. Peters
  • Asmund Rinnan
  • Werner W. Streicher
  • Christopher F. van der Walle
  • Shahid Uddin
  • Gerhard Winter
  • Dierk Roessner
  • Pernille Harris
  • Wolfgang Friess

Abstract

The discovery and development of therapeutic proteins depend on reliable computational and biophysical characterization. Improvement of this process requires knowledge and understanding of protein structure and behaviour as a function of solution conditions. Here, we share a dataset on a diverse group of therapeutically relevant proteins, including their primary sequences, purity data, and an extensive computational and biophysical characterization as a function of solution pH and ionic strength. We find only weak correlations between many of
the determined biophysical parameters, indicating that these are not interchangeable. Further, we comment that a stability comparison of diverse therapeutic protein candidates should be based on biophysical characterization in multiple solvent conditions. Finally, we use the presented dataset to calculate several stability risk scores obtained with an increasing level of analytical effort and show how they correlate with storage stability data.

Bibliographical metadata

Original languageEnglish
Pages (from-to)426-440
Number of pages15
JournalMolecular Pharmaceutics
Volume17
Issue number2
Early online date2 Dec 2019
DOIs
Publication statusPublished - Feb 2020

Related information

Researchers

View all