Synthesis and structure-activity relationship studies of IgG-binding peptides focused on the C-terminal histidine residue

Kyohei Muguruma; Mayu Ito; Akane Fukuda; Satoshi Kishimoto; Akihiro Taguchi; Kentaro Takayama; Atsuhiko Taniguchi; Yuji Ito; Yoshio Hayashi

doi:10.1039/c9md00294d

Synthesis and structure-activity relationship studies of IgG-binding peptides focused on the C-terminal histidine residue

Medchemcomm. 2019 Aug 1;10(10):1789-1795. doi: 10.1039/c9md00294d. eCollection 2019 Oct 1.

Authors

Kyohei Muguruma¹, Mayu Ito¹, Akane Fukuda¹, Satoshi Kishimoto², Akihiro Taguchi¹, Kentaro Takayama¹, Atsuhiko Taniguchi¹, Yuji Ito², Yoshio Hayashi¹

Affiliations

¹ Department of Medicinal Chemistry , Tokyo University of Pharmacy and Life Sciences , Hachioji , Tokyo , 192-0392 , Japan . Email: yhayashi@toyaku.ac.jp.
² Department of Chemistry and Bioscience , Graduate School of Science and Engineering , Kagoshima University , Korimoto , Kagoshima , 890-0065 , Japan.

Abstract

Currently, IgG-binding peptides are widely utilized as a research tool, as molecules that guide substrates to the Fc site for site-selective antibody modification, leading to preparation of a homogeneous antibody-drug conjugate. In this study, a structure-activity relationship study of an IgG-binding peptide, 15-IgBP, that is focused on its C-terminal His residue was performed in an attempt to create more potent peptides. A peptide with a substitution of His17 by 2-pyridylalanine (2-Pya) showed a good binding affinity (15-His17(2-Pya), K _d = 75.7 nM). In combination with a previous result, we obtained 15-Lys8Leu/His17(2-Pya)-OH that showed a potent binding affinity (K _d = 2.48 nM) and avoided three synthetic problems concerning the p-hydroxybenzyl amidation at the C-terminus, the difficulty associated with coupling at the His7 position and the racemization of 2-Pya.