Design, Synthesis, and Biological Evaluation of Small, High-Affinity Siglec-7 Ligands: Toward Novel Inhibitors of Cancer Immune Evasion

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autor(en): Prescher H, Frank M, Guetgemann S, Kuhfeldt E, Schweizer A, Nitschke L, Watzl C, Brossmer R
Zeitschrift: Journal of Medicinal Chemistry
Verlag: AMER CHEMICAL SOC
Jahr der Veröffentlichung: 2017
Band: 60
Heftnummer: 3
Seitenbereich: 941-956
ISSN: 0022-2623


Abstract


Natural killer cells are able to directly lyse tumor cells, thereby participating in the immune surveillance against cancer. Unfortunately,, many cancer-cells use immune evasion strategies to avoid their eradication by the immune system. A prominent escape-strategy of malignant cells is to camouflage themselves with Siglec-7 ligands, thereby recruiting the inhibitory receptor Siglec-7 expressed On the NK cell surface which subsequently inhibits NK-cell-mediated lysis. Here we describe the synthesis and:evaluation of the first, high-affinity low molecular weight Siglec-7 ligands to interfere with cancer tell immune evasion. The compounds are Sialic acid derivatives and bind with low inicromolar K-d values to Siglec-7. They display up to a 5000-fold enhanced affinity over the unmodified sight acid scaffold alpha Me NeuSAc, the smallest known natural Siglec-7 ligand. Our results provide-a novel imanuno-oncology strategy employing natural immunity in the fight against cancers, in particular-blocking Siglec-7 with low:molecular weight compounds:



FAU-Autoren / FAU-Herausgeber

Nitschke, Lars Prof. Dr.
Professur für Genetik
Schweizer, Astrid Dr.
Sonderforschungsbereich 643 Strategien der zellulären Immunintervention (Sprecher: Prof.Dr.Schuler)


Autor(en) der externen Einrichtung(en)
Deutsches Krebsforschungszentrum (DKFZ)
Ruprecht-Karls-Universität Heidelberg


Zitierweisen

APA:
Prescher, H., Frank, M., Guetgemann, S., Kuhfeldt, E., Schweizer, A., Nitschke, L.,... Brossmer, R. (2017). Design, Synthesis, and Biological Evaluation of Small, High-Affinity Siglec-7 Ligands: Toward Novel Inhibitors of Cancer Immune Evasion. Journal of Medicinal Chemistry, 60(3), 941-956. https://dx.doi.org/10.1021/acs.jmedchem.6b01111

MLA:
Prescher, Horst, et al. "Design, Synthesis, and Biological Evaluation of Small, High-Affinity Siglec-7 Ligands: Toward Novel Inhibitors of Cancer Immune Evasion." Journal of Medicinal Chemistry 60.3 (2017): 941-956.

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Zuletzt aktualisiert 2018-06-08 um 20:38