Chemistry Commons^™

Guanidinium-Rich Romp Polymers Drive Phase, Charge, And Curvature-Specific Interactions With Phospholipid Membranes, Michael T W Lis

Doctoral Dissertations

Protein transduction domains (PTDs) and their and their synthetic mimics are short sequences capable of unusually high uptake in cells. Several varieties of these molecules, including the arginine-rich Tat peptide from HIV, have been extensively used as vectors for protein, DNA, and siRNA delivery into cells. Despite the wide-ranging utility of PTDs and their mimics, their uptake mechanism is still under considerable debate. How the molecules are able to cross phospholipid membranes, and what structural components are necessary for optimal activity are poorly understood. This thesis explores how PTDMs interact with phospholipid membrane phase, anionic lipid content and negative Gaussian …

Quantum Mechanics In Complex Systems, Ross Douglas Hoehn

Open Access Dissertations

This document should be considered in its separation; there are three distinct topics contained within and three distinct chapters within the body of works. In a similar fashion, this abstract should be considered in three parts. Firstly, we explored the existence of multiply-charged atomic ions by having developed a new set of dimensional scaling equations as well as a series of relativistic augmentations to the standard dimensional scaling procedure and to the self-consistent field calculations. Secondly, we propose a novel method of predicting drug efficacy in hopes to facilitate the discovery of new small molecule therapeutics by modeling the agonist-protein …

New Experimental And Theoretical Tools For Studying Protein Systems With Elements Of Structural Disorder, Tairan Yuwen

Open Access Dissertations

Disordered proteins are one class of proteins which do not possess well-folded three-dimensional structures as their native conformations. Many eukaryotic proteins have been found to be fully disordered or contain certain disordered regions. Disordered proteins usually display several characteristic properties, such as increased motional freedom and the conformational heterogeneity caused by that. The elements of structural disorder are commonly involved in many important biological functions and are implicated in many diseases. Therefore, the study of disordered proteins has become one of the most important research topics in recent years. This thesis presents results from three different research projects; the common …

Protein Behavior Directed By Heparin Charge And Chain Length, Burcu Baykal Minsky

Doctoral Dissertations

Glycosaminoglycans (GAGs), highly charged biological polyelectrolytes, are of growing importance as biomaterials and pharmaceutical drugs due to their immense range of physiological functions. They bind to many proteins; however, the degree of structural selectivity in GAG-protein interactions is largely unknown .Our studies have focused on the importance of heparin (a model GAG) charge and chain length in protein binding in order to explore its potential applications in biofunctional tissue scaffold materials, as polysaccharide drugs in anticoagulation, and as inhibitory agents in protein aggregation. We used electrospray ionization mass spectrometry, capillary electrophoresis, size exclusion chromatography, dynamic/static light scattering and electrostatic protein …

Interactions Of Eukaryotic Translation Initiation Factors And 3' Untranslated Region Of Barley Yellow Dwarf Virus Mrna During Protein Synthesis: A Study Of Equilibrium Binding, Kinetics And Thermodynamics, Bidisha Banerjee

Dissertations, Theses, and Capstone Projects

Eukaryotic initiation factor (eIF) 4F binding to mRNA is the first committed step in cap-dependent protein synthesis. Barley Yellow Dwarf Virus (BYDV) employs a cap-independent mechanism of translation initiation which is mediated by a structural element BTE (BYDV translation element) located in the 3’ UTR of its mRNA. eIF4F bound the BTE and a translational inactive mutant with high affinity; thus questioning the role of eIF4F in translation of BYDV. To examine the effects of eIF4F in BYDV translation initiation, BTE mutants with widely different in vitro translation efficiencies ranging from 5-164% compared to WT were studied. Using fluorescence anisotropy …

Combination Of The Computational Methods: Molecular Dynamics, Homology Modeling And Docking To Design Novel Inhibitors And Study Structural Changes In Target Proteins For Current Diseases, Katherine Cristina Parra

USF Tampa Graduate Theses and Dissertations

In this thesis, molecular dynamics simulations, molecular docking, and homology modeling methods have been used in combination to design possible inhibitors as well as to study the structural changes and function of target proteins related to diseases that today are in the spotlight of drug discovery. The inwardly rectifying potassium (Kir) channels constitute the first target in this study; they are involved in cardiac problems. On the other hand, tensin, a promising target in cancer research, is the second target studied here.

The first chapter includes a brief update on computational methods and the current proposal of the combination of …

Conformational Features Of The Human U2-U6 Snrna Complex, Ravichandra Bachu

Dissertations, Theses, and Capstone Projects

The splicing of precursor messenger (pre-m) RNA, during which noncoding intervening sequences are excised and flanking coding regions ligated, is an integral reaction of gene expression. In eukaryotes, it is carried out by a dynamic RNA-protein complex called the spliceosome, in which five small nuclear (sn) RNA components are actively involved in recognition and chemical aspects of the process. A complex formed between U2 and U6 snRNAs is implicated in the chemistry of pre-mRNA splicing. The catalytic activity of the U2-U6 snRNA complex is dependent on the presence of Mg2+ ions, and the complex has been shown to have several …

Hiv-1 Rna Dimerization At Single Molecule Level, Hansini R. Mundigala

Wayne State University Dissertations

The Dimerization Initiation Sequence (DIS) is a conserved hairpin-loop motif on the 5' UTR of the HIV-1 genome. It plays an important role in genome dimerization through formation of a "kissing complex" intermediate between two homologous DIS sequences. This bimolecular kissing complex ultimately leads to the formation of an extended RNA duplex. Understanding the kinetics of this interaction is key to exploiting DIS as a possible drug target against HIV. We wish to report a novel study that makes an important contribution to understanding the dimerization mechanism of HIV-1 RNA in vitro. Our work has employed single-molecule fluorescence resonance energy …

Characterization Of Initial Iron Binding Location And The Structure/Iron Binding Site On S.Cerevisiae Isu And On D.Melanogaster Frataxin, Andria V. Rodrigues

Wayne State University Dissertations

Iron-induced free radical damage has been implicated in the pathology of diseases of iron overload such as Friedreich's Ataxia, a genetic disorder characterized by an accumulation of iron in actively metabolizing tissues ultimately leading to cardio- and neuro- degeneration and cell death. It is caused by an inability to synthesize the mitochondrial protein, frataxin. Frataxin has been shown by numerous groups to be a part of the iron-sulfur cluster (ISC) multicomplex, where it functions in the capacity of a potential iron provider and an allosteric modulator of both the cysteine desulfurase and scaffold protein ISU. My research has been focused …