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Enhancing the pharmaceutical properties of protein drugs by ancestral sequence reconstruction.
Zakas, Philip M; Brown, Harrison C; Knight, Kristopher; Meeks, Shannon L; Spencer, H Trent; Gaucher, Eric A; Doering, Christopher B.
Afiliación
  • Zakas PM; Program in Molecular and Systems Pharmacology, Laney Graduate School, Emory University, Atlanta, Georgia, USA.
  • Brown HC; Program in Molecular and Systems Pharmacology, Laney Graduate School, Emory University, Atlanta, Georgia, USA.
  • Knight K; Aflac Cancer and Blood Disorders Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA.
  • Meeks SL; Aflac Cancer and Blood Disorders Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA.
  • Spencer HT; Program in Molecular and Systems Pharmacology, Laney Graduate School, Emory University, Atlanta, Georgia, USA.
  • Gaucher EA; Aflac Cancer and Blood Disorders Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA.
  • Doering CB; School of Biology, Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, Georgia, USA.
Nat Biotechnol ; 35(1): 35-37, 2017 Jan.
Article en En | MEDLINE | ID: mdl-27669166
ABSTRACT
Optimization of a protein's pharmaceutical properties is usually carried out by rational design and/or directed evolution. Here we test an alternative approach based on ancestral sequence reconstruction. Using available genomic sequence data on coagulation factor VIII and predictive models of molecular evolution, we engineer protein variants with improved activity, stability, and biosynthesis potential and reduced inhibition by anti-drug antibodies. In principle, this approach can be applied to any protein drug based on a conserved gene sequence.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor VIII / Ingeniería de Proteínas / Proteínas / Secuencia Conservada / Sinergismo Farmacológico / Descubrimiento de Drogas Tipo de estudio: Prognostic_studies Idioma: En Revista: Nat Biotechnol Asunto de la revista: BIOTECNOLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor VIII / Ingeniería de Proteínas / Proteínas / Secuencia Conservada / Sinergismo Farmacológico / Descubrimiento de Drogas Tipo de estudio: Prognostic_studies Idioma: En Revista: Nat Biotechnol Asunto de la revista: BIOTECNOLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos