Structure Derivatization of IgG-Binding Peptides and Analysis of Their Secondary Structure by Circular Dichroism Spectroscopy
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- Muguruma Kyohei
- Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences
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- Fukuda Akane
- Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences
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- Shida Hayate
- Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences
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- Taguchi Akihiro
- Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences
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- Takayama Kentaro
- Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences
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- Taniguchi Atsuhiko
- Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences
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- Ito Yuji
- Department of Chemistry and Bioscience, Graduate School of Science and Engineering, Kagoshima University
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- Hayashi Yoshio
- Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences
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Description
<p>Mid-sized cyclic peptides are a promising modality for modern drug discovery. Their larger interaction area coupled with an appropriate secondary structure is more suitable than small molecules for binding to the target protein. In this study, we conducted a structure derivatization of an immunoglobulin G (IgG)-binding peptide (15-IgBP), a β-hairpin-like cyclic peptide with a twisted β-strand and assessed the effect of the secondary structure on IgG-binding activity using circular dichroism (CD) spectra analysis. As a result, derivatization at the Ala5 and Gly9 positions affected the secondary structure of 15-IgBP, in particular the appearance of a small positive peak in the 220–240 nm region characteristic of 15-IgBP in the CD spectrum. Maintaining this peak at a moderate level may be important for the expression of IgG binding activity. We found the small methyl group at Ala5 to be crucial for retaining the preferred secondary structure; we also found Gly9 could be replaced by D-amino acids. By integrating these findings with previous results of the structure–activity relationship, we obtained four potent affinity peptides for IgG binding (Kd = 4.24–5.85 nM). Furthermore, we found the Gly9 position can be substituted for D-Lys. This is a new potential site for attaching functional units for conjugation with IgG for the preparation of homogeneous antibody–drug conjugates.</p>
Journal
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- Chemical and Pharmaceutical Bulletin
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Chemical and Pharmaceutical Bulletin 72 (9), 831-837, 2024-09-20
The Pharmaceutical Society of Japan
