Structure-based design of supercharged, highly thermoresistant antibodies

Aleksandr E. Miklos, Christien Kluwe, Bryan S. Der, Supriya Pai, Aroop Sircar, Randall A. Hughes, Monica Berrondo, Jianqing Xu, Vlad Codrea, Patricia E. Buckley, Alena M. Calm, Heather S. Welsh, Candice R. Warner, Melody A. Zacharko, James P. Carney, Jeffrey J. Gray, George Georgiou, Brian Kuhlman, Andrew D. Ellington

Producción científica: Articlerevisión exhaustiva

122 Citas (Scopus)

Resumen

Mutation of surface residues to charged amino acids increases resistance to aggregation and can enable reversible unfolding. We have developed a protocol using the Rosetta computational design package that "supercharges" proteins while considering the energetic implications of each mutation. Using a homology model, a single-chain variable fragment antibody was designed that has a markedly enhanced resistance to thermal inactivation and displays an unanticipated ≈30-fold improvement in affinity. Such supercharged antibodies should prove useful for assays in resource-limited settings and for developing reagents with improved shelf lives.

Idioma originalEnglish (US)
Páginas (desde-hasta)449-455
Número de páginas7
PublicaciónChemistry and Biology
Volumen19
N.º4
DOI
EstadoPublished - abr 20 2012
Publicado de forma externa

ASJC Scopus subject areas

  • Drug Discovery
  • Molecular Medicine
  • Molecular Biology
  • Biochemistry
  • Clinical Biochemistry
  • Pharmacology

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