Identification of specific carbonic anhydrase inhibitors via in situ click chemistry, phage-display and synthetic peptide libraries: comparison of the methods and structural study
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F23%3A00565749" target="_blank" >RIV/61388963:_____/23:00565749 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11310/23:10467031
Result on the web
<a href="https://doi.org/10.1039/D2MD00330A" target="_blank" >https://doi.org/10.1039/D2MD00330A</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1039/d2md00330a" target="_blank" >10.1039/d2md00330a</a>
Alternative languages
Result language
angličtina
Original language name
Identification of specific carbonic anhydrase inhibitors via in situ click chemistry, phage-display and synthetic peptide libraries: comparison of the methods and structural study
Original language description
The development of highly active and selective enzyme inhibitors is one of the priorities of medicinal chemistry. Typically, various high-throughput screening methods are used to find lead compounds from a large pool of synthetic compounds, and these are further elaborated and structurally refined to achieve the desired properties. In an effort to streamline this complex and laborious process, new selection strategies based on different principles have recently emerged as an alternative. Herein, we compare three such selection strategies with the aim of identifying potent and selective inhibitors of human carbonic anhydrase II. All three approaches, in situ click chemistry, phage-display libraries and synthetic peptide libraries, led to the identification of more potent inhibitors when compared to the parent compounds. In addition, one of the inhibitor-peptide conjugates identified from the phage libraries showed greater than 100-fold selectivity for the enzyme isoform used for the compound selection. In an effort to rationalize the binding properties of the conjugates, we performed detailed crystallographic and NMR structural analysis, which revealed the structural basis of the compound affinity towards the enzyme and led to the identification of a novel exosite that could be utilized in the development of isoform specific inhibitors.
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
10609 - Biochemical research methods
Result continuities
Project
<a href="/en/project/EF16_019%2F0000729" target="_blank" >EF16_019/0000729: Chemical biology for drugging undruggable targets</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
RSC MEDICINAL CHEMISTRY
ISSN
2632-8682
e-ISSN
2632-8682
Volume of the periodical
14
Issue of the periodical within the volume
1
Country of publishing house
GB - UNITED KINGDOM
Number of pages
10
Pages from-to
144-153
UT code for WoS article
000891927700001
EID of the result in the Scopus database
2-s2.0-85143545117