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@ARTICLE{Prescher:119829,
author = {H. Prescher and M. Frank$^*$ and S. Gütgemann and E.
Kuhfeldt and A. Schweizer and L. Nitschke and C. Watzl and
R. Brossmer},
title = {{D}esign, {S}ynthesis, and {B}iological {E}valuation of
{S}mall, {H}igh-{A}ffinity {S}iglec-7 {L}igands: {T}oward
{N}ovel {I}nhibitors of {C}ancer {I}mmune {E}vasion.},
journal = {Journal of medicinal chemistry},
volume = {60},
number = {3},
issn = {1520-4804},
address = {Washington, DC},
publisher = {ACS},
reportid = {DKFZ-2017-00424},
pages = {941 - 956},
year = {2017},
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 cell immune evasion. The compounds
are Sialic acid derivatives and bind with low micromolar Kd
values to Siglec-7. They display up to a 5000-fold enhanced
affinity over the unmodified sialic acid scaffold αMe
Neu5Ac, the smallest known natural Siglec-7 ligand. Our
results provide a novel immuno-oncology strategy employing
natural immunity in the fight against cancers, in particular
blocking Siglec-7 with low molecular weight compounds.},
cin = {W160},
ddc = {540},
cid = {I:(DE-He78)W160-20160331},
pnm = {314 - Tumor immunology (POF3-314)},
pid = {G:(DE-HGF)POF3-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:28103033},
doi = {10.1021/acs.jmedchem.6b01111},
url = {https://inrepo02.dkfz.de/record/119829},
}