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Pustuła, M.* ; Czub, M.* ; Łabuzek, B.* ; Surmiak, E.* ; Tomala, M.* ; Twarda-Clapa, A.* ; Guzik, K.* ; Popowicz, G.M. ; Holak, T.A.*

NMR fragment-based screening for development of the CD44-binding small molecules.

Bioorg. Chem. 82, 284-289 (2019)
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Open Access Green
The cell-surface protein CD44, a primary receptor for hyaluronic acid (HA), is one of the most promising targets for cancer therapies. It is prominently involved in the process of tumor growth and metastasis. The possibility of modulating the CD44-HA interaction with a pharmacological inhibitor is therefore of great importance, yet until now there are only few small molecules reported to bind to CD44. Here, we describe the results of the NMR fragment-based screening conducted against CD44 by which we found eight new hit compounds that bind to the receptor with the affinity in milimolar range. The NMR-based characterization revealed that there are two possible binding modes for these compounds, and for some of them the binding is no longer possible in the presence of hyaluronic acid. This could provide an interesting starting point for the development of new high-affinity ligands targeting the CD44-HA axis.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Cd44 ; Hyaluronic Acid ; Small-molecular Inhibitors ; Fragment-based Screening; Cell-surface Receptor; Chemical-shift Perturbation; Bivatuzumab Mertansine; Colorectal-cancer; Cd44 Expression; Binding Domain; Breast-cancer; Adhesion; Carcinoma; Antibody
ISSN (print) / ISBN 0045-2068
e-ISSN 1090-2120
Zeitschrift Bioorganic chemistry
Quellenangaben Band: 82, Heft: , Seiten: 284-289 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort San Diego, Calif.
Begutachtungsstatus Peer reviewed