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Date of Award
Campus Access Dissertation
Doctor of Philosophy in Chemistry (PhD)
Administrative Home Department
Department of Chemistry
Tarun K. Dam
Committee Member 1
Committee Member 2
Committee Member 3
Lectins are carbohydrate or glycan binding proteins produced by every living species. Binding of lectins to glycan epitopes of glycoproteins is essential for initiating a variety of biological functions. Galectin-3 (Gal-3) is an endogenous human lectin that plays important roles in cell proliferation, adhesion, differentiation, metastasis, angiogenesis, and apoptosis. This dissertation describes two new binding properties of Gal-3 that are physiologically relevant. The new interaction of Gal-3 described herein significantly extends its biological function. Biological interactions of Gal-3 are known to occur when it binds to glycoproteins. However, we found that Gal-3 also binds to another class of glycoconjugates, namely, proteoglycans and their constituent glycosaminoglycans. Calorimetric data show that Gal-3 binds with glycosaminoglycans (heparin and chondroitin sulfate) and chondroitin sulfate proteoglycans (CSGPs). Spectroscopic data reveal that Gal-3 cross-links with chondroitin sulfate A and C as well as a CSGP and forms insoluble complexes. Such cross-linking of Gal-3 by glycosaminoglycans is potentially important for many biological processes including cell-signaling. We also discovered that Gal-3, produced by malignant thyroid gland, interacts with a thyroid cancer biomarker, thyroglobulin (Tg) with nanomolar affinity. This interaction can interfere with the clinical detection of thyroid cancer and can also impact thyroid hormone production and immune response. To produce sufficient Gal-3 for these studies, a new purification protocol named ‘Capture and Release’ (CARE) was developed. This protocol is cost-effective, faster and was found to be efficient enough to purify other lectins besides Gal-3. The function of lectins including Gal-3, depends on the interaction with their binding partners (glycoconjugates). Glycoconjugate is a common name of any macromolecule that contains glycans linked to a protein or lipid core (scaffold). The outcome of lectin-glycoconjugate interactions is believed to depend solely on the structures of the lectin and the glycan epitopes. However, we discovered that the scaffold part plays a vital role in the binding process. This dissertation thus describes a novel molecular mechanism associated with glycoconjugate functions and new physiologically-relevant recognition properties of an important human lectin (Gal-3).
Talaga, Melanie, "Novel Carbohydrate-Dependent Biological Properties of Human Health Related Lectins and Glycoconjugates", Campus Access Dissertation, Michigan Technological University, 2016.