Computational Evolution of Threonine-Rich β-Hairpin Peptides Mimicking Specificity and Affinity of Antibodies
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Computational Evolution of Threonine-Rich β-Hairpin Peptides Mimicking Specificity and Affinity of Antibodies. / Hu, Hongxia; Kofoed, Christian; Li, Ming; Gonçalves, Juliana Pereira Lopes; Hansen, Jonas; Wolfram, Martin; Hansen, Axel Kornerup; Friis Hansen, Camilla Hartmann; Diness, Frederik; Schoffelen, Sanne; Meldal, Morten.
I: ACS Central Science, Bind 5, Nr. 2, 27.02.2019, s. 259-269.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Computational Evolution of Threonine-Rich β-Hairpin Peptides Mimicking Specificity and Affinity of Antibodies
AU - Hu, Hongxia
AU - Kofoed, Christian
AU - Li, Ming
AU - Gonçalves, Juliana Pereira Lopes
AU - Hansen, Jonas
AU - Wolfram, Martin
AU - Hansen, Axel Kornerup
AU - Friis Hansen, Camilla Hartmann
AU - Diness, Frederik
AU - Schoffelen, Sanne
AU - Meldal, Morten
PY - 2019/2/27
Y1 - 2019/2/27
N2 - The development of recognition molecules with antibody-like properties is of great value to the biotechnological and bioanalytical communities. The recognition molecules presented here are peptides with a strong tendency to form β-hairpin structures, stabilized by alternate threonines, which are located at one face of the peptide. Amino acids at the other face of the peptide are available for interaction with the target molecule. Using this scaffold, we demonstrate that recognition molecules can efficiently be designed in silico toward four structurally unrelated proteins, GFP, IL-1β, IL-2, and IL-6. On solid support, 10 different antibody-mimetic recognition molecules were synthesized. They displayed high affinity and no cross-reactivity, as observed by fluorescence microscopy. Stabilized variants were readily obtained by incorporation of azido acids and propargylglycine followed by cyclization via the Cu(I)-catalyzed alkyne-azide cycloaddition reaction. As this new class of antibody mimics can be designed toward essentially any protein, the concept is believed to be useful to a wide range of technologies. Here, their use in protein separation and in the detection of proteins in a sandwich-type assay is demonstrated.
AB - The development of recognition molecules with antibody-like properties is of great value to the biotechnological and bioanalytical communities. The recognition molecules presented here are peptides with a strong tendency to form β-hairpin structures, stabilized by alternate threonines, which are located at one face of the peptide. Amino acids at the other face of the peptide are available for interaction with the target molecule. Using this scaffold, we demonstrate that recognition molecules can efficiently be designed in silico toward four structurally unrelated proteins, GFP, IL-1β, IL-2, and IL-6. On solid support, 10 different antibody-mimetic recognition molecules were synthesized. They displayed high affinity and no cross-reactivity, as observed by fluorescence microscopy. Stabilized variants were readily obtained by incorporation of azido acids and propargylglycine followed by cyclization via the Cu(I)-catalyzed alkyne-azide cycloaddition reaction. As this new class of antibody mimics can be designed toward essentially any protein, the concept is believed to be useful to a wide range of technologies. Here, their use in protein separation and in the detection of proteins in a sandwich-type assay is demonstrated.
U2 - 10.1021/acscentsci.8b00614
DO - 10.1021/acscentsci.8b00614
M3 - Journal article
C2 - 30834314
AN - SCOPUS:85061225946
VL - 5
SP - 259
EP - 269
JO - A C S Central Science
JF - A C S Central Science
SN - 2374-7943
IS - 2
ER -
ID: 231361390