Use of uteroglobin for the engineering of polyvalent, polyspecific fusion proteins

Elisa Ventura, Francesca Sassi, Sara Fossati, Arianna Parodi, William Blalock, Enrica Balza, Patrizia Castellani, Laura Borsi, Barbara Carnemolla, Luciano Zardi

Research output: Contribution to journalArticlepeer-review

Abstract

We report a novel strategy to engineer and express stable and soluble human recombinant polyvalent/polyspecific fusion proteins. The procedure is based on the use of a central skeleton of uteroglobin, a small and very soluble covalently linked homodimeric protein that is very resistant to proteolytic enzymes and to pH variations. Using a human recombinant antibody (scFv) specific for the angiogenesis marker domain B of fibronectin, interleukin 2, and an scFv able to neutralize tumor necrosis factor-α, we expressed various biologically active uteroglobin fusion proteins. The results demonstrate the possibility to generate monospecific divalent and tetravalent antibodies, immunocytokines, and dual specificity tetravalent antibodies. Furthermore, compared with similar fusion proteins in which uteroglobin was not used, the use of uteroglobin improved properties of solubility and stability. Indeed, in the reported cases it was possible to vacuum dry and reconstitute the proteins without any aggregation or loss in protein and biological activity.

Original languageEnglish
Pages (from-to)26646-26654
Number of pages9
JournalJournal of Biological Chemistry
Volume284
Issue number39
DOIs
Publication statusPublished - Sep 25 2009

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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