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dc.contributor.advisorRimer, Jeffrey D.
dc.creatorFarmanesh, Sahar
dc.date.accessioned2016-02-21T01:22:10Z
dc.date.available2016-02-21T01:22:10Z
dc.date.createdDecember 2013
dc.date.issued2013-12
dc.identifier.urihttp://hdl.handle.net/10657/1220
dc.description.abstractPathological biomineralization is believed to be regulated in vivo by the interaction of urinary constituents with crystal interfaces. Here we examine the role of native and biomimetic growth modifiers of calcium oxalate monohydrate (COM), which is the most prevalent crystalline constituent of human kidney stones. Many proteins and glycosaminoglycans in urine are putative growth inhibitors and display an affinity for binding to specific surfaces of COM crystals to suppress their growth (and aggregation) in vivo. We have examined some of the most common constituents identified by proteomic studies of the organic matrix of human stones. These studies reveal a range of COM crystal inhibitors and promoters. To characterize their efficacy and specificity for binding to COM crystal surfaces, we used a combination of experimental techniques to quantify the effects of these urinary constituents on COM crystal size, habit, surface architecture, and growth kinetics. Results of these studies reveal that certain binary combinations of urinary components exhibit a synergetic enhancement of their efficacy, while other combinations yielded antagonistic effects. Using the most effective urinary proteins as inspiration, we designed and tested small peptides as COM growth modifiers (i.e., biomimetic analogues). We developed a platform to design, synthesize, and screen peptide libraries to measure their efficacy for inhibiting COM crystallization. Our results show that subtle variations in amino acid sequences and composition have a profound effect on growth inhibition. Collectively, these studies are a basis for ongoing initiatives to design novel drug candidates for kidney stone disease and a generalized platform for the rational design of inorganic and advanced materials with tailored properties.
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.rightsThe author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).
dc.subjectCrystal growth
dc.subjectCalcium Oxalate Monohydrate
dc.subjectModifiers
dc.subjectProteins
dc.subjectPeptide
dc.subjectCombination Index
dc.subjectGrowth Inhibitor
dc.subjectGrowth Promoter
dc.subjectDrug design
dc.subjectKidney stone
dc.subjectRenal health
dc.subjectKidney health
dc.subjectInorganic materials
dc.titleROLE OF NATURAL AND SYNTHETIC GROWTH MODIFIERS IN CALCIUM OXALATE MONOHYDRATE CRYSTALLIZATION
dc.date.updated2016-02-21T01:22:10Z
dc.type.genreThesis
thesis.degree.nameDoctor of Philosophy
thesis.degree.levelDoctoral
thesis.degree.disciplineChemical Engineering
thesis.degree.grantorUniversity of Houston
thesis.degree.departmentChemical and Biomolecular Engineering, Department of
dc.contributor.committeeMemberVekilov, Peter G.
dc.contributor.committeeMemberWillson, Richard C.
dc.contributor.committeeMemberChellam, Shankar
dc.contributor.committeeMemberMiljanić, Ognjen Š.
dc.type.dcmiText
dc.format.digitalOriginborn digital
dc.description.departmentChemical and Biomolecular Engineering, Department of
thesis.degree.collegeCullen College of Engineering


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