 Chemical tools for epichaperome-mediated interactome dysfunctions of the central nervous systemAlexander Bolaender,
Danuta Zatorska,
Huazhong He,
Suhasini Joshi,
Sahil Sharma,
Chander S. Digwal,
Hardik J. Patel,
Weilin Sun,
Brandon S. Imber,
Stefan O. Ochiana,
Maulik R. Patel,
Liza Shrestha,
Smit. K. Shah,
Shuo Wang,
Rashad Karimov,
Hui Tao,
Pallav D. Patel,
Ananda Rodilla Martin,
Pengrong Yan,
Palak Panchal,
Justina Almodovar,
Adriana Corben,
Andreas Rimner,
Stephen D. Ginsberg,
Serge Lyashchenko,
Eva Burnazi,
Anson Ku,
Teja Kalidindi,
Sang Gyu Lee,
Milan Grkovski,
Bradley J. Beattie,
Pat Zanzonico,
Jason S. Lewis,
Steve Larson,
Anna Rodina,
Nagavarakishore Pillarsetty,
Viviane Tabar,
Mark P. Dunphy,
Tony Taldone,
Fumiko Shimizu () and
Gabriela Chiosis ()
Nature Communications, 2021, vol. 12, issue 1, 1-19 Abstract: Abstract Diseases are a manifestation of how thousands of proteins interact. In several diseases, such as cancer and Alzheimer’s disease, proteome-wide disturbances in protein-protein interactions are caused by alterations to chaperome scaffolds termed epichaperomes. Epichaperome-directed chemical probes may be useful for detecting and reversing defective chaperomes. Here we provide structural, biochemical, and functional insights into the discovery of epichaperome probes, with a focus on their use in central nervous system diseases. We demonstrate on-target activity and kinetic selectivity of a radiolabeled epichaperome probe in both cells and mice, together with a proof-of-principle in human patients in an exploratory single group assignment diagnostic study (ClinicalTrials.gov Identifier: NCT03371420). The clinical study is designed to determine the pharmacokinetic parameters and the incidence of adverse events in patients receiving a single microdose of the radiolabeled probe administered by intravenous injection. In sum, we introduce a discovery platform for brain-directed chemical probes that specifically modulate epichaperomes and provide proof-of-principle applications in their use in the detection, quantification, and modulation of the target in complex biological systems. Date: 2021 Downloads: (external link) Related works: Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24821-2 Ordering information: This journal article can be ordered from DOI: 10.1038/s41467-021-24821-2 Access Statistics for this article Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie More articles in Nature Communications from Nature |
Is your work missing from RePEc? Here is how to contribute.
Questions or problems? Check the EconPapers FAQ or send mail to .
EconPapers is hosted by the
School of Business at Örebro University.