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An antibody CDR3-erythropoietin fusion protein

Academic Article
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Overview

authors

  • Zhang, Y.
  • Wang, D. L.
  • Welzel, G.
  • Wang, Y.
  • Schultz, Peter
  • Wang, F.

publication date

  • October 2013

journal

  • ACS Chemical Biology  Journal

abstract

  • X-ray crystallographic analysis of a bovine antibody (BLV1H12) revealed a unique scaffold in its ultralong heavy chain complementarity determining region 3 (CDR3H) that folds into a solvent exposed, antiparallel β-stranded "stalk" fused with a disulfide cross-linked "knob" domain. This unusual variable region motif provides a novel approach for generating chimeric antibodies with novel activities. Toward this end, human erythropoietin (hEPO) was substituted for the "knob" domain in this antibody to afford an antibody-hEPO (Ab-hEPO) fusion protein that efficiently expresses in mammalian cells. Ab-hEPO proliferated TF-1 cells with a potency comparable to that of hEPO (EC50 ∼ 0.03 nM) and exhibits a significantly extended plasma half-life (>6 days) in mice relative to hEPO (∼4 h). Mice treated with the Ab-hEPO fusion protein show sustained elevated hematocrit for more than two weeks. This work demonstrates the utility of BLV1H12 CDR3 fusions as a novel approach for generating potent polypeptides with enhanced pharmacological properties.

subject areas

  • Administration, Intravenous
  • Animals
  • Cattle
  • Cell Line
  • Cell Survival
  • Crystallography, X-Ray
  • Enzyme-Linked Immunosorbent Assay
  • Erythropoietin
  • Humans
  • Immunoglobulin G
  • Mice
  • Recombinant Fusion Proteins
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Identity

PubMed Central ID

  • PMC3800483

International Standard Serial Number (ISSN)

  • 1554-8929

Digital Object Identifier (DOI)

  • 10.1021/cb4004749

PubMed ID

  • 23941200
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Additional Document Info

start page

  • 2117

end page

  • 2121

volume

  • 8

issue

  • 10

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