Ligand Strain and Its Conformational Complexity Is a Major Factor in the Binding of Cyclic Dinucleotides to STING Protein
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F21%3A00541558" target="_blank" >RIV/61388963:_____/21:00541558 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1002/anie.202016805" target="_blank" >https://doi.org/10.1002/anie.202016805</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/anie.202016805" target="_blank" >10.1002/anie.202016805</a>
Alternative languages
Result language
angličtina
Original language name
Ligand Strain and Its Conformational Complexity Is a Major Factor in the Binding of Cyclic Dinucleotides to STING Protein
Original language description
STING (stimulator of interferon genes) is a key regulator of innate immunity that has recently been recognized as a promising drug target. STING is activated by cyclic dinucleotides (CDNs) which eventually leads to expression of type I interferons and other cytokines. Factors underlying the affinity of various CDN analogues are poorly understood. Herein, we correlate structural biology, isothermal calorimetry (ITC) and computational modeling to elucidate factors contributing to binding of six CDNs—three pairs of natural (ribo) and fluorinated (2′‐fluororibo) 3′,3′‐CDNs. X‐ray structural analyses of six {STING:CDN} complexes did not offer any explanation for the different affinities of the studied ligands. ITC showed entropy/enthalpy compensation up to 25 kcal mol−1 for this set of similar ligands. The higher affinities of fluorinated analogues are explained with help of computational methods by smaller loss of entropy upon binding and by smaller strain (free) energy.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10403 - Physical chemistry
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Angewandte Chemie - International Edition
ISSN
1433-7851
e-ISSN
1521-3773
Volume of the periodical
60
Issue of the periodical within the volume
18
Country of publishing house
DE - GERMANY
Number of pages
7
Pages from-to
10172-10178
UT code for WoS article
000631782200001
EID of the result in the Scopus database
2-s2.0-85103176233