%0 Journal Article
%A Sagini, Micah N
%A Klika, Karel D
%A Orry, Andrew
%A Zepp, Michael
%A Mutiso, Joshua
%A Berger, Martin
%T Riproximin Exhibits Diversity in Sugar Binding, and Modulates some Metastasis-Related Proteins with Lectin like Properties in Pancreatic Ductal Adenocarcinoma.
%J Frontiers in pharmacology
%V 11
%@ 1663-9812
%C Lausanne
%I Frontiers Media
%M DKFZ-2020-02954
%P 549804
%D 2020
%Z #EA:G401#LA:G401#
%X Riproximin (Rpx) is a type II ribosome-inactivating protein with specific anti-proliferative activity. It was purified from Ximenia americana by affinity chromatography using a resin coupled with lactosyl residues. The same technique facilitated isolation of proteins with lectin-like properties from human Suit2-007 and rat ASML pancreatic cancer cells, which were termed lactosyl-sepharose binding proteins (LSBPs). The role of these proteins in cancer progression was investigated at mRNA level using chip array data of Suit2-007 and ASML cells re-isolated from nude rats. These data compared significant mRNA expression changes when relating primary (pancreas) and metastatic (liver) sites following orthotopic and intraportal implantation of Pancreatic Ductal Adenocarcinoma (PDAC) cells, respectively. The affinity of Rpx to 13 simple sugar structures was modeled by docking experiments, the ranking of which was principally confirmed by NMR-spectroscopy. In addition, Rpx and LSBPs were evaluated for anti-proliferative activity and their cellular uptake was assessed by fluorescence microscopy. From 13 monosaccharides evaluated, open-chain rhamnose, β-d-galactose, and α-l-galactopyranose showed the highest affinities for site 1 of Rpx's B-chain. NMR evaluation yielded a similar ranking, as galactose was among the best binders. Both, Rpx and LSBPs reduced cell proliferation in vitro, but their anti-proliferative effects were decreased by 15-20
%K Pancreatic ductal adenocarcinoma (Other)
%K affinity  (Other)
%K cellular lectins (Other)
%K lactosyl-sepharose binding proteins (Other)
%K monosaccharides (Other)
%K ribosome-inactivating protein (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:33328982
%2 pmc:PMC7734336
%R 10.3389/fphar.2020.549804
%U https://inrepo02.dkfz.de/record/166511