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Building a Better Dynasore: The Dyngo Compounds Potently Inhibit Dynamin and Endocytosis
Author(s) -
McCluskey Adam,
Daniel James A.,
Hadzic Gordana,
Chau Ngoc,
Clayton Emma L.,
Mariana Anna,
Whiting Ainslie,
Gorgani Nick N.,
Lloyd Jonathan,
Quan Annie,
Moshkanbaryans Lia,
Krishnan Sai,
Perera Swetha,
Chircop Megan,
von Kleist Lisa,
McGeachie Andrew B.,
Howes Mark T.,
Parton Robert G.,
Campbell Michael,
Sakoff Jennette A.,
Wang Xuefeng,
Sun JianYuan,
Robertson Mark J.,
Deane Fiona M.,
Nguyen Tam H.,
Meunier Frederic A.,
Cousin Michael A.,
Robinson Phillip J.
Publication year - 2013
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/tra.12119
Subject(s) - dynamin , endocytosis , cytotoxicity , biophysics , potency , biology , microbiology and biotechnology , biochemistry , receptor mediated endocytosis , in vitro , cell
Dynamin is essential for clathrin‐mediated endocytosis ( CME ). We describe the Dyngo™ series of dynamin inhibitors with greatly improved potency, reduced cytotoxicity and reduced detergent binding compared to their parent, dynasore. Dyngo compound 4a is 37‐fold more potent for dynamin inhibition and at least sixfold more potent for CME inhibition in cells and nerve terminals. This series are the first to target one conformational state of dynamin, inhibiting lipid‐associated helical dynamin but not dynamin rings induced by self‐assembly or SH3 ‐domain‐containing proteins.