Rational Design of a New Class of Toll-Like Receptor 4 (TLR4) Tryptamine Related Agonists by Means of the Structure- and Ligand-Based Virtual Screening for Vaccine Adjuvant Discovery
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F18%3A50014338" target="_blank" >RIV/62690094:18470/18:50014338 - isvavai.cz</a>
Alternative codes found
RIV/00179906:_____/18:10373139 RIV/61988987:17110/18:A1901RU1
Result on the web
<a href="http://www.mdpi.com/1420-3049/23/1/102" target="_blank" >http://www.mdpi.com/1420-3049/23/1/102</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3390/molecules23010102" target="_blank" >10.3390/molecules23010102</a>
Alternative languages
Result language
angličtina
Original language name
Rational Design of a New Class of Toll-Like Receptor 4 (TLR4) Tryptamine Related Agonists by Means of the Structure- and Ligand-Based Virtual Screening for Vaccine Adjuvant Discovery
Original language description
In order to identify novel lead structures for human toll-like receptor 4 (hTLR4) modulation virtual high throughput screening by a peta-flops-scale supercomputer has been performed. Based on the in silico studies, a series of 12 compounds related to tryptamine was rationally designed to retain suitable molecular geometry for interaction with the hTLR4 binding site as well as to satisfy general principles of drug-likeness. The proposed compounds were synthesized, and tested by in vitro and ex vivo experiments, which revealed that several of them are capable to stimulate hTLR4 in vitro up to 25% activity of Monophosphoryl lipid A. The specific affinity of the in vitro most potent substance was confirmed by surface plasmon resonance direct-binding experiments. Moreover, two compounds from the series show also significant ability to elicit production of interleukin 6.
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
30107 - Medicinal chemistry
Result continuities
Project
<a href="/en/project/GA15-11776S" target="_blank" >GA15-11776S: Rational design of novel immunomodulators - potential vaccine adjuvans - based on TLR4 ligands</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Molecules
ISSN
1420-3049
e-ISSN
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Volume of the periodical
23
Issue of the periodical within the volume
1
Country of publishing house
CH - SWITZERLAND
Number of pages
19
Pages from-to
1-19
UT code for WoS article
000425082500097
EID of the result in the Scopus database
2-s2.0-85040557257