Open AccessIsolation of antigen-specific, disulphide-rich knob domain peptides from bovine antibodies
Author(s) -
Alex Macpherson,
Anthony Scott-Tucker,
Anastasios Spiliotopoulos,
Cathy A. Simpson,
Justin Staniforth,
Adam Hold,
James Snowden,
Leah Manning,
Jean M. H. van den Elsen,
Alastair D. G. Lawson
Publication year - 2020
Publication title -
plos biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.127
H-Index - 271
eISSN - 1545-7885
pISSN - 1544-9173
DOI - 10.1371/journal.pbio.3000821
Subject(s) - antibody , biology , peptide , antigen , single domain antibody , computational biology , peptide library , drug discovery , function (biology) , biochemistry , peptide sequence , microbiology and biotechnology , immunology , gene
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.