Many therapeutic proteins possessing a small size are rapidly cleared from circulation. Half-life extension strategies have therefore become increasingly important to improve the pharmacokinetic and pharmacodynamic properties of protein therapeutics. Here, we performed a comparative analysis of the half-life extension properties of various bacterial immunoglobulin-binding domains (IgBDs) derived from Staphylococcus protein A (SpA), Streptococcus protein G (SpG), and Finegoldia (formerly Peptostreptococcus) protein L (PpL). These domains, composed of 50-60 amino acid residues, were fused to the C terminus of a single-chain Fv and a bispecific single-chain diabody, respectively. All fusion proteins were produced in mammalian cells and retained their antigen-binding properties. The half-lives of the antibody molecules were prolonged to varying extents for the different IgBDs. The strongest effects in mice were observed for domain C3 of SpG (SpG(C3)) followed by domains B and D of SpA, suggesting that SpG(C3) is particularly useful to extend the plasma half-life of small proteins.
%0 Journal Article
%1 Hutt2012
%A Hutt, Meike
%A Färber-Schwarz, Aline
%A Unverdorben, Felix
%A Richter, Fabian
%A Kontermann, Roland E.
%D 2012
%J Journal of Biological Chemistry
%K 2012 izi kontermann
%N 7
%P 4462--4469
%R 10.1074/jbc.M111.311522
%T Plasma half-life extension of small recombinant antibodies by fusion to immunoglobulin-binding domains
%U http://www.ncbi.nlm.nih.gov/pubmed/22147690
%V 287
%X Many therapeutic proteins possessing a small size are rapidly cleared from circulation. Half-life extension strategies have therefore become increasingly important to improve the pharmacokinetic and pharmacodynamic properties of protein therapeutics. Here, we performed a comparative analysis of the half-life extension properties of various bacterial immunoglobulin-binding domains (IgBDs) derived from Staphylococcus protein A (SpA), Streptococcus protein G (SpG), and Finegoldia (formerly Peptostreptococcus) protein L (PpL). These domains, composed of 50-60 amino acid residues, were fused to the C terminus of a single-chain Fv and a bispecific single-chain diabody, respectively. All fusion proteins were produced in mammalian cells and retained their antigen-binding properties. The half-lives of the antibody molecules were prolonged to varying extents for the different IgBDs. The strongest effects in mice were observed for domain C3 of SpG (SpG(C3)) followed by domains B and D of SpA, suggesting that SpG(C3) is particularly useful to extend the plasma half-life of small proteins.
%@ 1083-351X (Electronic)$\backslash$r0021-9258 (Linking)
@article{Hutt2012,
abstract = {Many therapeutic proteins possessing a small size are rapidly cleared from circulation. Half-life extension strategies have therefore become increasingly important to improve the pharmacokinetic and pharmacodynamic properties of protein therapeutics. Here, we performed a comparative analysis of the half-life extension properties of various bacterial immunoglobulin-binding domains (IgBDs) derived from Staphylococcus protein A (SpA), Streptococcus protein G (SpG), and Finegoldia (formerly Peptostreptococcus) protein L (PpL). These domains, composed of 50-60 amino acid residues, were fused to the C terminus of a single-chain Fv and a bispecific single-chain diabody, respectively. All fusion proteins were produced in mammalian cells and retained their antigen-binding properties. The half-lives of the antibody molecules were prolonged to varying extents for the different IgBDs. The strongest effects in mice were observed for domain C3 of SpG (SpG(C3)) followed by domains B and D of SpA, suggesting that SpG(C3) is particularly useful to extend the plasma half-life of small proteins.},
added-at = {2018-02-01T16:22:21.000+0100},
author = {Hutt, Meike and F{\"{a}}rber-Schwarz, Aline and Unverdorben, Felix and Richter, Fabian and Kontermann, Roland E.},
biburl = {https://puma.ub.uni-stuttgart.de/bibtex/27dbaf8af4ff61676c1ce25ed1739f663/cristiano},
doi = {10.1074/jbc.M111.311522},
interhash = {58e592791aa097a94b89738cceeab1e0},
intrahash = {7dbaf8af4ff61676c1ce25ed1739f663},
isbn = {1083-351X (Electronic)$\backslash$r0021-9258 (Linking)},
issn = {00219258},
journal = {Journal of Biological Chemistry},
keywords = {2012 izi kontermann},
month = feb,
number = 7,
pages = {4462--4469},
pmid = {22147690},
timestamp = {2019-01-17T13:18:14.000+0100},
title = {{Plasma half-life extension of small recombinant antibodies by fusion to immunoglobulin-binding domains}},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22147690},
volume = 287,
year = 2012
}
