dc.contributor.author
Cummer, Rebecca
dc.contributor.author
Bhatt, Garvit
dc.contributor.author
Finn, Lauren M.
dc.contributor.author
Keller, Bettina G.
dc.contributor.author
Nagar, Bhushan
dc.contributor.author
Castagner, Bastien
dc.date.accessioned
2025-06-27T10:55:28Z
dc.date.available
2025-06-27T10:55:28Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/47532
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-47250
dc.description.abstract
Inositol phosphates are essential for mammalian cell signalling with critical roles in cellular processes. The fully phosphorylated inositol phosphate, myo-inositol hexakisphosphate (IP6), modulates numerous eukaryotic proteins and bacterial virulence factors. It has been suggested that the high charge density of IP6 causes restructuring of virulence factors in mammalian cells, activating their enzymatic activity. IP6 is challenging to study due to its phytase instability and propensity to precipitate. Here we suggest that the thiophosphate bioisostere, myo-inositol hexakisthiophosphate (IT6), will mitigate these issues, as thiophosphate substitution has been found to be phytase resistant and improve solubility. Assessment of the chemical properties of IT6 has indeed validated these characteristics. In addition, we performed biophysical characterization of IT6 binding to the virulence factors Salmonella enterica serovar Typhimurium AvrA, Vibrio parahaemolyticus VopA, and Clostridioides difficile TcdB. Our data show that the higher charge density of IT6 increased its binding affinity and residence time on the proteins, which improved stabilization of the bound-state. IT6 is a valuable tool for structural biology research and the described biophysical characteristics of thiophosphate substitution are of value in medicinal chemistry.
en
dc.format.extent
9 Seiten
dc.rights.uri
https://creativecommons.org/licenses/by-nc/4.0/
dc.subject
inositol phosphates
en
dc.subject
thiophosphate bioisosteres
en
dc.subject
inositol hexakisphosphate
en
dc.subject.ddc
500 Naturwissenschaften und Mathematik::540 Chemie::540 Chemie und zugeordnete Wissenschaften
dc.title
Thiophosphate bioisosteres of inositol hexakisphosphate enhance binding affinity and residence time on bacterial virulence factors
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.doi
10.1039/D4CB00228H
dcterms.bibliographicCitation.journaltitle
RSC Chemical Biology
dcterms.bibliographicCitation.number
6
dcterms.bibliographicCitation.pagestart
882
dcterms.bibliographicCitation.pageend
890
dcterms.bibliographicCitation.volume
6
dcterms.bibliographicCitation.url
https://doi.org/10.1039/D4CB00228H
refubium.affiliation
Biologie, Chemie, Pharmazie
refubium.affiliation.other
Institut für Chemie und Biochemie

refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.eissn
2633-0679
refubium.resourceType.provider
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