Discovery of a fluorescigenic pyrazoline derivative targeting ubiquitin

XinPeng Chen; ZhaoMin Lin; Le Su; XiaoLing Cui; BaoXiang Zhao; JunYing Miao

doi:10.1016/j.bbrc.2020.05.142

Discovery of a fluorescigenic pyrazoline derivative targeting ubiquitin

Biochem Biophys Res Commun. 2020 Jul 23;528(2):256-260. doi: 10.1016/j.bbrc.2020.05.142. Epub 2020 May 27.

Authors

XinPeng Chen¹, ZhaoMin Lin², Le Su³, XiaoLing Cui³, BaoXiang Zhao⁴, JunYing Miao⁵

Affiliations

¹ Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan, 250100, China; Hubei Key Laboratory of Edible Wild Plants Conservation & Utilization, School of Life Science, Hubei Normal University, Huangshi, 435002, PR China.
² Institute of Medical Science, The Second Hospital of Shandong University, Jinan, 250033, PR China.
³ Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan, 250100, China.
⁴ Institute of Organic Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan, 250100, China. Electronic address: bxzhao@sdu.edu.cn.
⁵ Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan, 250100, China; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, 250012, China. Electronic address: miaojy@sdu.edu.cn.

PMID: 32473753
DOI: 10.1016/j.bbrc.2020.05.142

Abstract

Despite significant process in ubiquitin modification by using traditional genetic methods, chemical small molecules that directly target and modify ubiquitin are little reported. Here, we find that a fluorescigenic pyrazoline derivative (FPD5) could do so effectively. Molecule docking revealed that lysine 11 of ubiquitin was the key contact residue. FPD5, with stronger fluorescence, elevated the ubiquitination of beclin 1 (BECN1) and promoted autophagy. This study highlights that targeting ubiquitin by chemical small molecules enables us to modulate ubiquitination and the downstream signaling in the ubiquitin system.

Keywords: Autophagy; BECN1; Fluorescigenic pyrazoline derivatives; Ubiquitin.

Publication types

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

MeSH terms

A549 Cells
Autophagy
Beclin-1 / metabolism
Fluorescence
HEK293 Cells
HeLa Cells
Humans
Lysine / metabolism
Pyrazoles / chemistry
Pyrazoles / metabolism*
Ubiquitin / metabolism*
Ubiquitination

Substances

Beclin-1
Pyrazoles
Ubiquitin
Lysine