Identification of Guanine-Quadruplex-Binding Peptides from the RGG3 Domain of TLS/FUS

Sayuri Takeo; Maiko Tabata; Hikari Okita; Natsuki Shibata; Kohei Sato; Nobuyuki Mase; Takanori Oyoshi; Tetsuo Narumi

doi:10.1248/cpb.c25-00413

Regular Article

Identification of Guanine-Quadruplex-Binding Peptides from the RGG3 Domain of TLS/FUS

Sayuri Takeo, Maiko Tabata, Hikari Okita, Natsuki Shibata, Kohei Sato, Nobuyuki Mase, Takanori Oyoshi , Tetsuo Narumi

著者情報

Sayuri Takeo
Graduate School of Medical Photonics, Shizuoka University, 3–5–1 Johoku, Chuo-ku, Hamamatsu 432–8011, Japan
Maiko Tabata
Graduate School of Integrated Science and Technology, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka 422–8529, Japan
Hikari Okita
Department of Applied Chemistry and Biochemical Engineering, Faculty of Engineering, Shizuoka University, 3–5–1 Johoku, Chuo-ku, Hamamatsu 432–8011, Japan
Natsuki Shibata
Graduate School of Integrated Science and Technology, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka 422–8529, Japan
Kohei Sato
Department of Applied Chemistry and Biochemical Engineering, Faculty of Engineering, Shizuoka University, 3–5–1 Johoku, Chuo-ku, Hamamatsu 432–8011, Japan
Research Institute of Green Science and Technology, Shizuoka University, 3–5–1 Johoku, Chuo-ku, Hamamatsu 432–8011, Japan
Nobuyuki Mase
Department of Applied Chemistry and Biochemical Engineering, Faculty of Engineering, Shizuoka University, 3–5–1 Johoku, Chuo-ku, Hamamatsu 432–8011, Japan
Research Institute of Green Science and Technology, Shizuoka University, 3–5–1 Johoku, Chuo-ku, Hamamatsu 432–8011, Japan
Takanori Oyoshi 責任著者
Graduate School of Integrated Science and Technology, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka 422–8529, Japan
Research Institute of Green Science and Technology, Shizuoka University, 3–5–1 Johoku, Chuo-ku, Hamamatsu 432–8011, Japan
Tetsuo Narumi 責任著者
Graduate School of Medical Photonics, Shizuoka University, 3–5–1 Johoku, Chuo-ku, Hamamatsu 432–8011, Japan
Department of Applied Chemistry and Biochemical Engineering, Faculty of Engineering, Shizuoka University, 3–5–1 Johoku, Chuo-ku, Hamamatsu 432–8011, Japan
Research Institute of Green Science and Technology, Shizuoka University, 3–5–1 Johoku, Chuo-ku, Hamamatsu 432–8011, Japan

キーワード: guanine quadruplex (G-quadruplex), peptide library, peptidomimetics, methylalkene dipeptide isostere, RNA binding

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2025 年 73 巻 10 号 p. 938-943

DOI https://doi.org/10.1248/cpb.c25-00413

詳細

抄録

Guanine quadruplexes (G4s) are non-canonical nucleic acid structures that have emerged as attractive therapeutic targets owing to their involvement in diverse biological processes. Additionally, peptides derived from G4-binding proteins provide promising platforms for selective G4 recognition. In this study, we explored the G4-binding capacity of arginine–glycine–glycine (RGG)-rich sequences derived from the RGG3 domain translocated in liposarcoma/fused in sarcoma (TLS/FUS), a known G4 RNA binding protein. In this study, we synthesized a library of overlapping 15-mer peptides and evaluated their G4-binding affinities. Among the 10 evaluated native sequences, several peptides demonstrated measurable affinities toward G4 RNA structures, with STK5-1 exhibiting the highest G4-binding affinity. Furthermore, to investigate the impact of conformational constraints on G4 recognition, we introduced (E)-methylalkene dipeptide isosteres (MADIs) into selected Gly–Gly motifs, generating a series of RGG peptidomimetics. Subsequent binding assays revealed that some of these MADI peptidomimetics exhibited enhanced affinity and selectivity compared with their unmodified counterparts. Our findings offer new insights into the sequence and structural features governing G4-binding, establishing a foundation for the further development of peptide-based G4 ligands.

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責任著者(Corresponding author)

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