TY - JOUR
T1 - A Strategy for Discovering Heterochiral Bioactive Peptides by Using the OB2nP Library and SPOTs Method
AU - Udagawa, Hinako
AU - Yoneda, Takato H.
AU - Masuda, Ryo
AU - Koide, Takaki
N1 - Funding Information:
This work was supported, in part, by Waseda University Grant for Special Research Project 2018B-195. We thank Drs. Masashi Kusubata, Yuki Taga, and Shunji Hattori (Nippi Inc.) for peptide sequencing. We also thank Yuki Yamauchi for preliminary experiments regarding this work.
Funding Information:
This work was supported, in part, by Waseda University Grant for Special Research Project 2018B-195. We thank Drs. Masashi Kusu-bata, Yuki Taga, and Shunji Hattori (Nippi Inc.) for peptide sequencing. We also thank Yuki Yamauchi for preliminary experiments regarding this work.
Publisher Copyright:
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2019/8/16
Y1 - 2019/8/16
N2 - d-Amino acid containing peptides are promising as drug lead compounds because of their expected higher stability in vivo. A heterochiral random peptide library called the one-bead–2n-peptide (OB2nP) library, which can display 2n peptide diastereomers per bead, has been developed. Through screening of the OB2nP library and subsequent binding assay among the peptide diastereomers synthesized in parallel by means of the SPOTs method, new heterochiral mimotopes for the anti-β-endorphin monoclonal antibody have been obtained. One mimotope was a new ligand for the μ-opioid receptor. The screening strategy enabled d-amino acid containing drug leads to be obtained efficiently by expanding searchable chemical space without increasing the experimental scale.
AB - d-Amino acid containing peptides are promising as drug lead compounds because of their expected higher stability in vivo. A heterochiral random peptide library called the one-bead–2n-peptide (OB2nP) library, which can display 2n peptide diastereomers per bead, has been developed. Through screening of the OB2nP library and subsequent binding assay among the peptide diastereomers synthesized in parallel by means of the SPOTs method, new heterochiral mimotopes for the anti-β-endorphin monoclonal antibody have been obtained. One mimotope was a new ligand for the μ-opioid receptor. The screening strategy enabled d-amino acid containing drug leads to be obtained efficiently by expanding searchable chemical space without increasing the experimental scale.
KW - combinatorial chemistry
KW - drug discovery
KW - heterochiral peptides
KW - high-throughput screening
KW - solid-phase synthesis
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U2 - 10.1002/cbic.201900237
DO - 10.1002/cbic.201900237
M3 - Article
C2 - 31111638
AN - SCOPUS:85069692360
SN - 1439-4227
VL - 20
SP - 2070
EP - 2073
JO - ChemBioChem
JF - ChemBioChem
IS - 16
ER -