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An antibody CDR3-erythropoietin fusion protein.

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.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Zhang Y,Wang D,Welzel G,Wang Y,Schultz PG,Wang F

doi

10.1021/cb4004749

subject

Has Abstract

pub_date

2013-10-18 00:00:00

pages

2117-21

issue

10

eissn

1554-8929

issn

1554-8937

journal_volume

8

pub_type

杂志文章

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