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Isolation of antigen-specific, disulphide-rich knob domain peptides from bovine antibodies
As a novel alternative to established surface display or combinatorial chemistry approaches for the discovery of therapeutic peptides, we present a method for the isolation of small, cysteine-rich domains from bovine antibody ultralong complementarity-determining regions (CDRs). We show for the firs...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498065/ https://www.ncbi.nlm.nih.gov/pubmed/32886672 http://dx.doi.org/10.1371/journal.pbio.3000821 |
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author | Macpherson, Alex Scott-Tucker, Anthony Spiliotopoulos, Anastasios Simpson, Catherine Staniforth, Justin Hold, Adam Snowden, James Manning, Leah van den Elsen, Jean Lawson, Alastair D. G. |
author_facet | Macpherson, Alex Scott-Tucker, Anthony Spiliotopoulos, Anastasios Simpson, Catherine Staniforth, Justin Hold, Adam Snowden, James Manning, Leah van den Elsen, Jean Lawson, Alastair D. G. |
author_sort | Macpherson, Alex |
collection | PubMed |
description | As a novel alternative to established surface display or combinatorial chemistry approaches for the discovery of therapeutic peptides, we present a method for the isolation of small, cysteine-rich domains from bovine antibody ultralong complementarity-determining regions (CDRs). We show for the first time that isolated bovine antibody knob domains can function as autonomous entities by binding antigen outside the confines of the antibody scaffold. This yields antibody fragments so small as to be considered peptides, each stabilised by an intricate, bespoke arrangement of disulphide bonds. For drug discovery, cow immunisations harness the immune system to generate knob domains with affinities in the picomolar to low nanomolar range, orders of magnitude higher than unoptimized peptides from naïve library screening. Using this approach, knob domain peptides that tightly bound Complement component C5 were obtained, at scale, using conventional antibody discovery and peptide purification techniques. |
format | Online Article Text |
id | pubmed-7498065 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-74980652020-09-24 Isolation of antigen-specific, disulphide-rich knob domain peptides from bovine antibodies Macpherson, Alex Scott-Tucker, Anthony Spiliotopoulos, Anastasios Simpson, Catherine Staniforth, Justin Hold, Adam Snowden, James Manning, Leah van den Elsen, Jean Lawson, Alastair D. G. PLoS Biol Methods and Resources As a novel alternative to established surface display or combinatorial chemistry approaches for the discovery of therapeutic peptides, we present a method for the isolation of small, cysteine-rich domains from bovine antibody ultralong complementarity-determining regions (CDRs). We show for the first time that isolated bovine antibody knob domains can function as autonomous entities by binding antigen outside the confines of the antibody scaffold. This yields antibody fragments so small as to be considered peptides, each stabilised by an intricate, bespoke arrangement of disulphide bonds. For drug discovery, cow immunisations harness the immune system to generate knob domains with affinities in the picomolar to low nanomolar range, orders of magnitude higher than unoptimized peptides from naïve library screening. Using this approach, knob domain peptides that tightly bound Complement component C5 were obtained, at scale, using conventional antibody discovery and peptide purification techniques. Public Library of Science 2020-09-04 /pmc/articles/PMC7498065/ /pubmed/32886672 http://dx.doi.org/10.1371/journal.pbio.3000821 Text en © 2020 Macpherson et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Methods and Resources Macpherson, Alex Scott-Tucker, Anthony Spiliotopoulos, Anastasios Simpson, Catherine Staniforth, Justin Hold, Adam Snowden, James Manning, Leah van den Elsen, Jean Lawson, Alastair D. G. Isolation of antigen-specific, disulphide-rich knob domain peptides from bovine antibodies |
title | Isolation of antigen-specific, disulphide-rich knob domain peptides from bovine antibodies |
title_full | Isolation of antigen-specific, disulphide-rich knob domain peptides from bovine antibodies |
title_fullStr | Isolation of antigen-specific, disulphide-rich knob domain peptides from bovine antibodies |
title_full_unstemmed | Isolation of antigen-specific, disulphide-rich knob domain peptides from bovine antibodies |
title_short | Isolation of antigen-specific, disulphide-rich knob domain peptides from bovine antibodies |
title_sort | isolation of antigen-specific, disulphide-rich knob domain peptides from bovine antibodies |
topic | Methods and Resources |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498065/ https://www.ncbi.nlm.nih.gov/pubmed/32886672 http://dx.doi.org/10.1371/journal.pbio.3000821 |
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