Date of Award
1-1-2024
Document Type
Dissertation
Degree Name
Ph.D. in Pharmaceutical Sciences
First Advisor
Vitor H. Pomin
Second Advisor
Marc Slattery
Third Advisor
Paul Boudreau
School
University of Mississippi
Relational Format
dissertation/thesis
Abstract
This dissertation presents a comprehensive analysis of various marine-derived polysaccharides, focusing on their structures and binding properties. Using nuclear magnetic resonance (NMR) and surface plasmon resonance (SPR), distinct marine polysaccharides were structurally characterized, and their interactions with various biological targets were evaluated. The initial study explores a glucan isolated from Marcia hiantina, a bivalve mollusk, and its biological activity. Detailed structural analysis via NMR and chromatography techniques revealed a branched glucose-based polysaccharide with potent antioxidant and anti-inflammatory properties. Further studies on the red alga Botryocladia occidentalis identified three sulfated galactans in its cell wall. Through NMR, we characterized the least sulfated polysaccharide, discovering unique methylation and sulfation patterns. SPR analysis indicated that this galactan interacts differently with anticoagulation factors compared to more heavily sulfated forms, demonstrating stronger binding to heparin cofactor II and weaker binding to thrombin and factor Xa. Expanding the scope, we examined marine sulfated glycans (MSGs) from diverse sources, including sea urchins and sea cucumbers, for their anticoagulant properties. Using SPR, MSGs were shown to modulate coagulation factor interactions independently of antithrombin, with zinc ions influencing these interactions. This highlights MSGs as promising anticoagulant agents with potential safety advantages over conventional therapies. Moreover, we assessed the sulfatase enzyme SULF2, which plays a role in cancer invasiveness by modifying heparan sulfate binding with growth factors. A study demonstrated that high fucosylated chondroitin sulfates (HfFucCS) inhibit SULF2, potentially mitigating cancer cell invasion, suggesting novel approaches in cancer therapeutics. We used SPR to study the inhibitory effect of native and depolymerized HfFucCS on SULF2. Finally, we used SPR to investigate the binding properties of Phallusia nigra dermatan sulfate (PnD2,6S) with basic fibroblast growth factor (bFGF), a critical factor in cellular growth and differentiation. This work elucidates the structure-activity relationship of PnD2,6S by comparing its binding dynamics with those of chondroitin sulfates and unfractionated heparin (UFH), revealing how specific structural features influence interactions with bFGF. In conclusion, the findings from this dissertation underscore the diverse structural complexities and biological activities of marine-derived polysaccharides. The integration of NMR and SPR methodologies provided valuable insights into their binding interactions, with implications for the development of new therapeutic agents. This work not only enhances our understanding of marine polysaccharides' roles in biomedical applications but also lays the groundwork for future research exploring their potential in drug development and disease modulation.
Recommended Citation
Ahmed, Hoda Alsayed Mohamed, "Structural and Binding Studies of Marine Glycans with Potential Therapeutic Use" (2024). Electronic Theses and Dissertations. 2996.
https://egrove.olemiss.edu/etd/2996
