Sulfonamide antibiotics inhibit RNAi by binding to human Argonaute protein 2 PAZ

Yoshiaki Kitamura; Mahmoud Kandeel; Tomoya Kondo; Akihiro Tanaka; Yohei Makino; Noriko Miyamoto; Aya Shibata; Masato Ikeda; Yukio Kitade

doi:10.1016/j.bmcl.2020.127637

Sulfonamide antibiotics inhibit RNAi by binding to human Argonaute protein 2 PAZ

Bioorg Med Chem Lett. 2020 Dec 15;30(24):127637. doi: 10.1016/j.bmcl.2020.127637. Epub 2020 Oct 22.

Authors

Yoshiaki Kitamura¹, Mahmoud Kandeel², Tomoya Kondo³, Akihiro Tanaka³, Yohei Makino³, Noriko Miyamoto⁴, Aya Shibata³, Masato Ikeda⁵, Yukio Kitade⁶

Affiliations

¹ Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan. Electronic address: kitamura@gifu-u.ac.jp.
² Department of Physiology, Biochemistry and Pharmacology, Faculty of Veterinary Medicine, King Faisal University, Al-Hofuf, Al-Ahsa 31982, Saudi Arabia; Department of Pharmacology, Faculty of Veterinary Medicine, Kafrelshikh University, Kafrelshikh 33516, Egypt.
³ Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
⁴ Department of Applied Chemistry, Faculty of Engineering, Aichi Institute of Technology, 1247 Yachigusa, Yakusa-cho, Toyota, Aichi 470-0392, Japan.
⁵ Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; Center for Highly Advanced Integration of Nano and Life Sciences, Gifu University (G-CHAIN), 1-1 Yanagido, Gifu 501-1193, Japan; Institute of Nano-Life-Systems, Institute of Innovation for Future Society, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8603, Japan; Institute for Glyco-core Research (iGCORE), Tokai National Higher Education and Research System, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8603, Japan.
⁶ Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; Department of Applied Chemistry, Faculty of Engineering, Aichi Institute of Technology, 1247 Yachigusa, Yakusa-cho, Toyota, Aichi 470-0392, Japan. Electronic address: ykkitade@aitech.ac.jp.

PMID: 33132114
DOI: 10.1016/j.bmcl.2020.127637

Abstract

We found that sulfisomidine, a sulfonamide antibiotic, potently binds to the Piwi/Argonaute/Zwille (PAZ) domain of human Argonaute protein 2 and inhibits RNA interference (RNAi). To elucidate the effect on RNAi of strong affinity of the 3'-ends in small interfering RNA (siRNA) to the PAZ domain, chemically modified siRNAs bearing sulfisomidine at the 3'-end were synthesized.

Keywords: Ago2; PAZ domain; RNAi; Sulfonamide antibiotics; siRNA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / pharmacology*
Argonaute Proteins / chemistry
Argonaute Proteins / metabolism*
Humans
Protein Domains / drug effects
RNA Interference / drug effects*
RNA, Small Interfering / antagonists & inhibitors
Sulfisomidine / pharmacology*
Sulfonamides / pharmacology

Substances

AGO2 protein, human
Anti-Bacterial Agents
Argonaute Proteins
RNA, Small Interfering
Sulfonamides
Sulfisomidine