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Rational Design of CXCR4 Specific Antibodies with Elongated CDRs
[Image: see text] The bovine antibody (BLV1H12) which has an ultralong heavy chain complementarity determining region 3 (CDRH3) provides a novel scaffold for antibody engineering. By substituting the extended CDRH3 of BLV1H12 with modified CXCR4 binding peptides that adopt a β-hairpin conformation,...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2014
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4120998/ https://www.ncbi.nlm.nih.gov/pubmed/25041362 http://dx.doi.org/10.1021/ja5042447 |
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author | Liu, Tao Liu, Yan Wang, Ying Hull, Mitchell Schultz, Peter G. Wang, Feng |
author_facet | Liu, Tao Liu, Yan Wang, Ying Hull, Mitchell Schultz, Peter G. Wang, Feng |
author_sort | Liu, Tao |
collection | PubMed |
description | [Image: see text] The bovine antibody (BLV1H12) which has an ultralong heavy chain complementarity determining region 3 (CDRH3) provides a novel scaffold for antibody engineering. By substituting the extended CDRH3 of BLV1H12 with modified CXCR4 binding peptides that adopt a β-hairpin conformation, we generated antibodies specifically targeting the ligand binding pocket of CXCR4 receptor. These engineered antibodies selectively bind to CXCR4 expressing cells with binding affinities in the low nanomolar range. In addition, they inhibit SDF-1-dependent signal transduction and cell migration in a transwell assay. Finally, we also demonstrate that a similar strategy can be applied to other CDRs and show that a CDRH2-peptide fusion binds CXCR4 with a K(d) of 0.9 nM. This work illustrates the versatility of scaffold-based antibody engineering and could greatly expand the antibody functional repertoire in the future. |
format | Online Article Text |
id | pubmed-4120998 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-41209982015-07-18 Rational Design of CXCR4 Specific Antibodies with Elongated CDRs Liu, Tao Liu, Yan Wang, Ying Hull, Mitchell Schultz, Peter G. Wang, Feng J Am Chem Soc [Image: see text] The bovine antibody (BLV1H12) which has an ultralong heavy chain complementarity determining region 3 (CDRH3) provides a novel scaffold for antibody engineering. By substituting the extended CDRH3 of BLV1H12 with modified CXCR4 binding peptides that adopt a β-hairpin conformation, we generated antibodies specifically targeting the ligand binding pocket of CXCR4 receptor. These engineered antibodies selectively bind to CXCR4 expressing cells with binding affinities in the low nanomolar range. In addition, they inhibit SDF-1-dependent signal transduction and cell migration in a transwell assay. Finally, we also demonstrate that a similar strategy can be applied to other CDRs and show that a CDRH2-peptide fusion binds CXCR4 with a K(d) of 0.9 nM. This work illustrates the versatility of scaffold-based antibody engineering and could greatly expand the antibody functional repertoire in the future. American Chemical Society 2014-07-18 2014-07-30 /pmc/articles/PMC4120998/ /pubmed/25041362 http://dx.doi.org/10.1021/ja5042447 Text en Copyright © 2014 American Chemical Society Terms of Use (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) |
spellingShingle | Liu, Tao Liu, Yan Wang, Ying Hull, Mitchell Schultz, Peter G. Wang, Feng Rational Design of CXCR4 Specific Antibodies with Elongated CDRs |
title | Rational
Design of CXCR4 Specific Antibodies with
Elongated CDRs |
title_full | Rational
Design of CXCR4 Specific Antibodies with
Elongated CDRs |
title_fullStr | Rational
Design of CXCR4 Specific Antibodies with
Elongated CDRs |
title_full_unstemmed | Rational
Design of CXCR4 Specific Antibodies with
Elongated CDRs |
title_short | Rational
Design of CXCR4 Specific Antibodies with
Elongated CDRs |
title_sort | rational
design of cxcr4 specific antibodies with
elongated cdrs |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4120998/ https://www.ncbi.nlm.nih.gov/pubmed/25041362 http://dx.doi.org/10.1021/ja5042447 |
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