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dc.contributor.advisorChairperson, Graduate Committee: Mary J. Cloningeren
dc.contributor.authorWolfenden, Mark Leroyen
dc.description.abstractPolyvalent interactions in biological systems have been of great interest recently; how nature creates high affinity polyvalent binding with low monomeric affinity, is yet to be clearly understood. We have created a bivalent lectincarbohydrate binding system using dendrimers as the carbohydrate mounted scaffold and Concanavalin A (Con A) as the mannose/glucose binding lectin to investigate this mode of interaction. The relative affinities of the utilized carbohydrates toward Con A are: mannose binds 4 times stronger than glucose, and galactose shows no affinity. With these relative affinities in hand and changing the ratios of mannose, glucose and galactose on the periphery of the PAMAM dendrimer scaffold, we have made a predictable and tuneable system with which to control the polyvalent binding relative affinity. By changing the carbohydrate presentation and varying the size of PAMAM dendrimer used, we can tune the affinity between two orders of magnitude. Although the relative affinities can be predictably altered, the clustering ability across the same generation dendrimer is not affected. In exploring more complex lectin : carbohydrate systems we have made a library of lactose, galactose and galNAc functionalized dendrimers to study binding to galectin-3. This lectin is implicated in numerous cancer related pathway, cellular proliferation and apoptosis. An ELISA based assay was developed to gain binding information of this intruiging interaction. The assay results suggest a reduced effect of binding association even with a large range of monomeric affinities, indicating a multivalent system. The monomer affinities did however affect the lectin recruitment to the dendrimers adsorbed onto a surface. The report here indicated a delicate interplay of modes of multivalent binding that dictate the biological behavior of this important galactose binding lectin.en
dc.publisherMontana State University - Bozeman, College of Letters & Scienceen
dc.subject.lcshOrganic compounds--Synthesisen
dc.titleUsing PAMAM dendrimer frameworks to investigate multivalent binding in protein-carbohydrate interactionsen
dc.rights.holderCopyright 2009 by Mark Leroy Wolfendenen
thesis.catalog.ckey1473875en, Graduate Committee: Brian Bothner; Thomas S. Livinghouse; Recep Avci; Robert K. Szilagyien & Biochemistry.en

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