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Full-Text Articles in Physical Sciences and Mathematics

Design Genetic Fluorescent Probes To Detect Protease Activity And Calcium-Dependent Protein-Protein Interactions In Living Cells, Ning Chen Aug 2008

Design Genetic Fluorescent Probes To Detect Protease Activity And Calcium-Dependent Protein-Protein Interactions In Living Cells, Ning Chen

Chemistry Dissertations

Proteases are essential for regulating a wide range of physiological and pathological processes. The imbalance of protease activation and inhibition will result in a number of major diseases including cancers, atherosclerosis, and neurodegenerative diseases. Although fluorescence resonance energy transfer (FRET)-based protease probes, a small molecular dye and other methods are powerful, they still have drawbacks or limitations for providing significant information about the dynamics and pattern of endogenous protease activation and inhibition in a single living cell or in vivo. Currently protease sensors capable of quantitatively measuring specific protease activity in real time and monitoring activation and inhibition of enzymatic …


The Design And Evaluation Of Boronic Acid Derivatives For The Recognition Of Cell Surface Carbohydrates For Medicinal Applications, Sandra Navonne Craig Aug 2008

The Design And Evaluation Of Boronic Acid Derivatives For The Recognition Of Cell Surface Carbohydrates For Medicinal Applications, Sandra Navonne Craig

Chemistry Dissertations

ABSTRACT Carbohydrates in various forms play vital roles in numerous critical biological processes including cell-cell adhesion and communication, embryo development, immune response, etc. Fluorescent sensors for such carbohydrates have a wide range of potential applications including glucose concentration determination, cell labeling and targeting based on carbohydrate biomarkers, as in vitro diagnostic tools, and biomarker-directed cellular imaging. Our group has been interested in the design and synthesis of multi-boronic acid compounds with well-defined three-dimensional scaffolding for the specific recognition of selected carbohydrate biomarkers. Aberrant expression of carbohydrate antigens such as sialyl Lewis X (sLex), sialyl Lewis A (sLea), Lewis X (Lex), …


Using Protein Design To Understand The Role Of Electrostatic Interactions On Calcium Binding Affinity And Molecular Recognition, Lisa Michelle Jones Aug 2008

Using Protein Design To Understand The Role Of Electrostatic Interactions On Calcium Binding Affinity And Molecular Recognition, Lisa Michelle Jones

Chemistry Dissertations

Calcium regulates many biological processes through interaction with proteins with different conformational, dynamic, and metal binding properties. Previous studies have shown that the electrostatic environment plays a key role in calcium binding affinity. In this research, we aim to dissect the contribution of the electrostatic environment to calcium binding affinity using protein design. Many natural calcium binding proteins undergo large conformational changes upon calcium binding which hampers the study of these proteins. In addition, cooperativity between multiple calcium binding sites makes it difficult to study site-specific binding affinity. The design of a single calcium binding site into a host system …


Determining The Site Specific Metal Binding And Structural Properties Of Ef-Hand Protein Using Grafting Approach, Hsiau-Wei Lee Aug 2008

Determining The Site Specific Metal Binding And Structural Properties Of Ef-Hand Protein Using Grafting Approach, Hsiau-Wei Lee

Chemistry Dissertations

Calmodulin is an essential EF-hand protein with a helix-loop-helix calcium binding motif. Understanding Ca(II) dependent activation of calmodulin and other EF-hand proteins is limited by Ca(II)-induced conformational change, multiple and cooperative binding of Ca(II) ions, and interactions between the paired EF-hand motifs. The goal of this research project is to probe key determinants for calcium binding properties and pairing interactions at the site specific level using a grafting approach and high resolution NMR. An individual Ca(II) binding site of the EF-hand motifs of calmodulin was grafted into a non-calcium dependent protein, CD2, to bypass limitations associated with natural EF-hand proteins …


Rational Design Of Calcium Biosensors, April L. Ellis Aug 2008

Rational Design Of Calcium Biosensors, April L. Ellis

Chemistry Dissertations

Understanding the temporal and spatial changes in calcium concentration has been a difficult endeavor for many years due to the relatively small changes in calcium concentration during messenging events, the rapid changes upon physiological messenging, and the unavailability of fast, efficient, and sensitive sensors to detect calcium changes. In addition, the key factors in calcium binding have yet to be determined due to the metal-metal interactions, cooperativity, and conformational change involved in calcium binding to natural calcium-binding proteins. To overcome these obstacles and to engineer calcium sensors for in vivo studies of calcium signaling events, calcium binding sites have been …


Structure And Energetics Of Rna - Protein Interactions For Hiv Rreiib Targeting Zinc Finger Proteins., Subrata H. Mishra Jul 2008

Structure And Energetics Of Rna - Protein Interactions For Hiv Rreiib Targeting Zinc Finger Proteins., Subrata H. Mishra

Chemistry Dissertations

RNA - protein interactions constitute a vital part of numerous biochemical processes. In the HIV life cycle, the interaction of the viral protein Rev and the Rev Responsive Element (RRE), a part of unspliced HIV RNA, is crucial for the propagation of infectious virions. Intervention of this interaction disrupts the viral life cycle. Rev - RRE interaction initially occurs at a high affinity binding site localized to a relatively small stem loop structure called RREIIB. This binding event has been well characterized by a variety of biochemical, enzymatic and structural studies. Our collaborators have previously demonstrated the efficacy of zinc …


Application Of Term-Rewriting Grammar In Chemical Reaction Prediction, Patra Volarath Apr 2008

Application Of Term-Rewriting Grammar In Chemical Reaction Prediction, Patra Volarath

Chemistry Dissertations

Synthesis planning is a critical process in chemical design. A number of computer programs have been developed to assist the chemists with this procedure. Most of the programs utilize combinations of computational approaches. These have been successfully applied to a number of the synthesis predictions. However, they require numerous rules to screen for potential targets, as well as to keep the system from reaching the combinatorial explosion. This results in the advanced algorithms becoming more complex and parameter-sensitive. This can be problematic, particularly in the cases in which a large number of the compounds are to be handled, because it …


Application Of Computer-Aided Drug Discovery Methodologies Towards The Rational Design Of Drugs Against Infectious Diseases, Prashanth Athri Apr 2008

Application Of Computer-Aided Drug Discovery Methodologies Towards The Rational Design Of Drugs Against Infectious Diseases, Prashanth Athri

Chemistry Dissertations

Computer-aided drug discovery involves the application of computer science and programming to solve chemical and biological problems. Specifically, the QSAR (Quantitative Structure Activity Relationships) methodology is used in drug development to provide a rational basis of drug synthesis, rather than a trial and error approach. Molecular dynamics (MD) studies focus on investigating the details of drug-target interactions to elucidate various biophysical characteristics of interest. Infectious diseases like Trypanosoma brucei rhodesiense (TBR) and P. falciparum (malaria) are responsible for millions of deaths annually around the globe. This necessitates an immediate need to design and develop new drugs that efficiently battle these …


I. Characterization Of Sulfonated Phthalocyanines By Mass Spectrometry. Ii. Characterization Of Siaa, A Streptococcal Heme-Binding Protein Associated With A Heme Abc Transport System, Brian R. Sook Apr 2008

I. Characterization Of Sulfonated Phthalocyanines By Mass Spectrometry. Ii. Characterization Of Siaa, A Streptococcal Heme-Binding Protein Associated With A Heme Abc Transport System, Brian R. Sook

Chemistry Dissertations

Sulfonated phthalocyanines were characterized using capillary electrophoresis and mass spectrometry. Derivatives investigated included the copper, cobalt, zinc and metal-free sulfonated phthalocyanines. The electropherograms of commercially available copper phthalocyanine-3,4',4'',4'''-tetrasulfonic acid and 4,4',4'',4'''-tetrasulfonic acid were very different, consistent with the latter compound having a structure that is not fully sulfonated. Matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI) were used to characterize the sulfonated phthalocyanines. Mass spectral evidence was obtained for a pentasulfonated species of both the metal-free phthalocyanine and zinc phthalocyanine when these species were made by sulfonation of the metal-free phthalocyanine (followed by zinc insertion in the latter case). Many …


Binding Studies Of Near Infrared Cyanine Dyes With Human Serum Albumin And Poly-L-Lysine Using Optical Spectroscopy Methods, Amy Dawn Watson Jan 2008

Binding Studies Of Near Infrared Cyanine Dyes With Human Serum Albumin And Poly-L-Lysine Using Optical Spectroscopy Methods, Amy Dawn Watson

Chemistry Dissertations

The sensitivity of biological studies performed between 190 and 650 nm is greatly reduced due to the autofluorescence of biomolecules and impurities in this region. Therefore, the enhanced signal-to-noise ratios encountered at longer wavelengths makes biological analysis within the near infrared (NIR) region from 650 nm to 1100 nm far more advantageous. This dissertation describes the noncovalent binding interactions of near-infrared (NIR) carbocyanine dyes with human serum albumin (HSA) and poly-L-lysine (PLL) using UV-Vis/NIR absorption spectroscopy, emission spectroscopy, circular dichroism (CD), and fluorescence detected circular dichroism (FDCD). The optical spectroscopy methods used in this work are described in detail in …