Tumor Carbohydrate Associated Antigen Analogs as Potential Binders for Siglec-7

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Tumor Carbohydrate Associated Antigen Analogs as Potential Binders for Siglec-7

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Tumor Carbohydrate Associated Antigen Analogs as Potential Binders for Siglec-7

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

<a href="/cs/project/LTC20078" target="_blank" >LTC20078: Glycan-dependent regulation of NK cell recognition: structural biology and novel methods of glycopeptide analysis</a><br>

Návaznosti

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

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

European Journal of Organic Chemistry

ISSN

1434-193X

e-ISSN

1099-0690

Svazek periodika

26

Číslo periodika v rámci svazku

40

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

8

Strana od-do

e202300644

Kód UT WoS článku

001064846500001

EID výsledku v databázi Scopus

2-s2.0-85170357638