21
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Antitumor agent calixarene 0118 targets human galectin-1 as an allosteric inhibitor of carbohydrate binding.

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Calix[4]arene compound 0118 is an angiostatic agent that inhibits tumor growth in mice. Although 0118 is a topomimetic of galectin-1-targeting angiostatic amphipathic peptide Anginex, we had yet to prove that 0118 targets galectin-1. Galectin-1 is involved in pathological disorders like tumor endothelial cell adhesion and migration and therefore presents a relevant target for therapeutic intervention against cancer. Here, (15)N-(1)H HSQC NMR spectroscopy demonstrates that 0118 indeed targets galectin-1 at a site away from the lectin's carbohydrate binding site and thereby attenuates lactose binding to the lectin. Flow cytometry and agglutination assays show that 0118 attenuates binding of galectin-1 to cell surface glycans, and the inhibition of cell proliferation by 0118 is found to be correlated with the cellular expression of the lectin. In general, our data indicate that 0118 targets galectin-1 as an allosteric inhibitor of glycan/carbohydrate binding. This work contributes to the clinical development of antitumor calixarene compound 0118.

          Related collections

          Author and article information

          Journal
          J. Med. Chem.
          Journal of medicinal chemistry
          1520-4804
          0022-2623
          Jun 14 2012
          : 55
          : 11
          Affiliations
          [1 ] Department of Biochemistry, Molecular Biology & Biophysics, University of Minnesota Health Sciences Center, 6-155 Jackson Hall, 321 Church Street, Minneapolis, Minnesota 55455, United States.
          Article
          NIHMS381819
          10.1021/jm300014q
          4242090
          22575017
          f7fd0940-bf12-4c23-adf1-f25f613c0f18
          History

          Comments

          Comment on this article