Structure-guided peptide engineering of a positive allosteric modulator targeting the outer pore of TRPV1 for long-lasting analgesia

Heng Zhang; Jia-Jia Lin; Ya-Kai Xie; Xiu-Zu Song; Jia-Yi Sun; Bei-Lei Zhang; Yun-Kun Qi; Zhen-Zhong Xu; Fan Yang

doi:10.1038/s41467-022-34817-1

Nature Communications (Jan 2023)

Structure-guided peptide engineering of a positive allosteric modulator targeting the outer pore of TRPV1 for long-lasting analgesia

Heng Zhang,
Jia-Jia Lin,
Ya-Kai Xie,
Xiu-Zu Song,
Jia-Yi Sun,
Bei-Lei Zhang,
Yun-Kun Qi,
Zhen-Zhong Xu,
Fan Yang

Affiliations

Heng Zhang: Department of Biophysics, Kidney Disease Center of the First Affiliated Hospital, Zhejiang University School of Medicine
Jia-Jia Lin: Liangzhu Laboratory, Zhejiang University Medical Center
Ya-Kai Xie: Liangzhu Laboratory, Zhejiang University Medical Center
Xiu-Zu Song: Department of Dermatology, The Third People’s Hospital of Hangzhou
Jia-Yi Sun: Department of Dermatology, The Third People’s Hospital of Hangzhou
Bei-Lei Zhang: Department of Dermatology, The Third People’s Hospital of Hangzhou
Yun-Kun Qi: Department of Medicinal Chemistry, School of Pharmacy, Qingdao University
Zhen-Zhong Xu: Liangzhu Laboratory, Zhejiang University Medical Center
Fan Yang: Department of Biophysics, Kidney Disease Center of the First Affiliated Hospital, Zhejiang University School of Medicine

DOI: https://doi.org/10.1038/s41467-022-34817-1
Journal volume & issue: Vol. 14, no. 1
pp. 1 – 12

Abstract

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TRPV1 as a drug target suffers from side effects of hypothermia. Here, authors engineer a peptide, sRhTx, as a positive allosteric modulator of TRPV1 channel. It potentiates the activity of TRPV1 to reversibly ablate pain-sensing nerve terminals for long-lasting analgesia without changing mice body temperature.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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