Tumor Carbohydrate Associated Antigen Analogs as Potential Binders for Siglec-7
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F23%3A10472847" target="_blank" >RIV/00216208:11310/23:10472847 - isvavai.cz</a>
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=g4koh-7jsK" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=g4koh-7jsK</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/ejoc.202300644" target="_blank" >10.1002/ejoc.202300644</a>
Alternative languages
Result language
angličtina
Original language name
Tumor Carbohydrate Associated Antigen Analogs as Potential Binders for Siglec-7
Original language description
We investigated two recently synthesized and characterized sialyl derivatives, bearing the Neu5Ac-a-(2-6)-Gal epitope, as promising binders for Siglec-7, an inhibitory Siglec mainly found on natural killer cells. A variety of sialoglycan structures can be recognized by Siglec-7 with implications in the modulation of immune responses. Notably, overexpression of sialylated glycans recognized by Siglec-7 can be associated with the progression of several tumors, including melanoma and renal cell carcinoma. NOE-based NMR techniques, including Saturation Transfer Difference and transferred-NOESY NMR, together with molecular docking and dynamic simulations were combined to shed light on the molecular basis of Siglec-7 recognition of two conformationally constrained Sialyl-Tn antigen analogs. We, therefore, identify the ligands epitope mapping and their conformational features and propose 3D models accurately describing the protein-ligand complexes. We found that the binding site of Siglec-7 can accommodate both synthetic analogs, with the sialic acid mainly involved in the interaction. Moreover, the flexibility of Siglec-7 loops allows a preferred accommodation of the more rigid compound bearing a biphenyl moiety at position 9 of the sialic acid that contributed to the interaction to a large extent. Our findings provided insights for developing potential novel high affinity ligands for Siglec-7 to hinder tumor evasion.
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
10401 - Organic chemistry
Result continuities
Project
<a href="/en/project/LTC20078" target="_blank" >LTC20078: Glycan-dependent regulation of NK cell recognition: structural biology and novel methods of glycopeptide analysis</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach<br>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
European Journal of Organic Chemistry
ISSN
1434-193X
e-ISSN
1099-0690
Volume of the periodical
26
Issue of the periodical within the volume
40
Country of publishing house
DE - GERMANY
Number of pages
8
Pages from-to
e202300644
UT code for WoS article
001064846500001
EID of the result in the Scopus database
2-s2.0-85170357638