Date of Completion


Embargo Period



Galectin-3, DX-52-1, Pulldown Assays, Mass Spectrometry, Structure–Activity Relationship

Major Advisor

Mark Peczuh

Associate Advisor

Challa Kumar

Associate Advisor

Xudong Yao

Associate Advisor

Robert Birge

Associate Advisor

Ronald Wikholm

Field of Study



Doctor of Philosophy

Open Access

Open Access


The Influence of DX-52-1 and Phosphorylation on the Interactions of Galectin-3 with its Binding Partners

Matthew L. Rotondi, PhD

University of Connecticut, 2015

Galectin-3, a member of a large family of animal based β-galactoside-binding lectins has been shown to play a role in a number of cellular and pathogenic processes. This protein has been shown throughout the literature to interact with a diverse multiplicity of proteins, involved in a diverse array of cellular functions, including cell migration and cell proliferation, both of which are of particular in regards to cancer research. Covalent modifications to Galectin-3 that can undermine its binding partner interactions would definitely prove useful in such an enterprise.

DX-52-1, a semisynthetic an analog of the natural product quinocarcin, has been shown by the Fenteany Group, to demonstrate remarkable anti-migration and anti-proliferation properties with regard to a number of cancer cell lines. Furthermore this molecule has been shown to bind strongly and specifically to Galectin-3 and Radixin. In the course of this research DX-52-1 has been shown to modestly undermine a number of binding partner interactions of Galectin-3. It has also been demonstrated that the phosphorylation of Galectin-3 also influences its binding to DX-52-1. It has been further demonstrated that DX-52-1 may have an even more potent effect on the formation of higher order complexes that contain Galectin-3. This observation may serve to further explain the strong anti-migration and anti-proliferation effects of DX-52-1.

In the course of this work, efforts to map the binding site of DX-52-1 on Galectin-3 were undertaken. In the course of those efforts a novel method to narrow down potential binding sites was developed. Furthermore structure activity relationship studies were performed to determine the importance of certain functional groups on the binding properties of DX-52-1 in regard to Galectin-3 and Radixin as wells as its anti-cellular properties. The results of these SAR studies show a link between the binding of DX-52-1 to Galectin-3 and its anti-migration and anti-proliferation properties.