Hybrid ligands with calixarene and thiodigalactoside groups: Galectin binding and cytotoxicity

Hao Zhang, Hans Ippel, Michelle C. Miller, Tse J. Wong, Arjan W. Griffioen, Kevin H. Mayo, Roland J. Pieters

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Galectins have diverse functions and are involved in many biological processes because of their complex intra- and extracellular activities. Selective and potent inhibitors for galectins will be valuable tools to investigate the biological functions of these proteins. Therefore, we describe here the synthesis of galectin inhibitors with a potential "chelate effect". These compounds are designed to bind to two different binding sites on galectins simultaneously. In this paper a series of asymmetric "hybrid" compounds are prepared, which combine two galectin ligands (1) a substituted thiodigalactoside derivative and (2) an antagonist calixarene-based therapeutic agent. NMR spectroscopy was used to evaluate the interactions of these compounds with Galectin-1 and -3. In addition, cellular experiments were conducted to compare the cytotoxic effects of the hybrids with those of a calixarene derivative. While only the thiodigalactoside part of the hybrids showed strong binding, the calixarene part was responsible for observed cytoxoxicity effects, suggesting that the calixarene moiety may also be addressing a non-galectin target.

Original languageEnglish (US)
Pages (from-to)2981-2990
Number of pages10
JournalOrganic Chemistry Frontiers
Issue number16
StatePublished - Aug 21 2019

Bibliographical note

Funding Information:
Hao Zhang gratefully acknowledge the financial support by a scholarship (file no. 201306210049) from the China Scholarship Council (http://www.csc.edu.cn/). We are very grateful to Prof. Guihua Tai for supplying us with isotopically-enriched galectins used in this study. We are also grateful to the Minnesota NMR Center and funding for NMR instrumentation from the Office of the Vice President for Research, the Medical School, the College of Biological Science, NIH, NSF, and the Minnesota Medical Foundation.

Publisher Copyright:
© the Partner Organisations 2019.


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