Biophysics Commons^™

Synthesis And Biophysical Analysis Of Modified Cell-Penetrating Peptides, Joel Mitchell

Theses and Dissertations (Comprehensive)

Cell-penetrating peptides (CPPs) are a family of peptides that have the ability to penetrate biological membranes. They were discovered in the late 1980s and have been the topic of many studies. Much of the interest in CPPs has been due to their ability to translocate biological membranes, and the possibility that they could offer a novel drug delivery method by conjugation to biologically active molecules. Linear CPPs can be modified to form cyclic structures. This change in structure has been observed to enhance the stability and penetrative ability of the CPPs which have been studied. The current thesis focuses on …

Exploring The Membrane Protein And Peptide Interactions Of Mitochondrial And Bacterial Lipid Systems, George Saudan

Theses and Dissertations (Comprehensive)

This study aims to expand the understanding of interactions between membrane lipids and proteins, and relate it to their biological functions in two experimental systems. The first system focuses on the interaction and conformation of a membrane protein Uncoupling Protein 4 (UCP4) in mitochondrial inner membrane lipids, in the absence and presence of cardiolipin; a lipid specific to mitochondrial inner membranes. The second system considers the interaction and conformation of a cell penetrating peptide, Penetratin, which can interact with both mammalian and bacterial cells. A N- and C-termini protected form of this 16-meric peptide (Pen2) was used to explore its …

On The Structure And Function Of Mitochondrial Uncoupling Proteins: The Case Of Ucp2, Afshan Ardalan

Theses and Dissertations (Comprehensive)

Uncoupling proteins (UCPs) are regulated proton transporters of the mitochondrial inner membrane. UCP-mediated proton leak negatively impacts the rate of ATP synthesis. Despite the importance of their physiological role(s) in certain tissues, molecular aspects of UCPs’ structure-function relationships are not fully understood. The current study explores the tertiary and quaternary structure of UCP2, as well as its proton transport mechanism in lipid membranes. The proteins were expressed in the E. coli inner membrane, purified and reconstituted into liposomes. Proteins were characterized by semi-native SDS-PAGE. Circular dichroism spectroscopy (CD) and fluorescence quenching assays were utilized to study the conformation of proteins …

Synthesis And Biophysical Analysis Of The Cell-Penetrating Peptide Penetratin And Its Aromatic Analogues, An Le

Theses and Dissertations (Comprehensive)

Cell-penetrating peptides (CPPs) interact with biological membranes, undergo cellular intake/uptake, and may act as potential drug delivery agents. Understanding the molecular interactions of these peptides with membranes contributes to gaining a better knowledge of their potential use in medical and pharmaceutical applications to improve human health. The current research focuses on understanding the mechanisms of a CPP in interaction with different model phospholipid membranes. The peptide penetratin (primary sequence: RQIKIWFQNRRMKWKK) is an example of a CPP that can interact with and pass through biological membranes. The current thesis provides spectroscopic and calorimetric evidence that penetratin associates with lipid membranes. Circular …

A Biophysical Study Of The Ion Transport Mechanism In Uncoupling Protein 2 By Investigating The Role Of Lysine Residues In Its Matrix Network, Stephanie O. Uwumarenogie

Theses and Dissertations (Comprehensive)

ABSTRACT

Uncoupling protein 2 (UCP2) is one of five UCP homologues found in the inner mitochondrial membrane that transports protons from the intermembrane space to the mitochondrial matrix. In turn, the proton motive force is dissipated and less ATP is produced in the mitochondria. UCP2 is proposed to influence insulin secretion in type II diabetes, and decrease the amount of reactive oxygen species produced in the mitochondria, however the detailed mechanism of ion (proton and anions) transport in UCP2 and other UCP homologues are not fully understood. Sequence alignment analysis performed on proteins in the mitochondrial carrier family (MCF) including …

Biophysical Characterization Of The Folding, Membrane Topology And Ion Transport Activity Of Ucp2 Using Selective Trp Mutants, Tyler C. Auld

Theses and Dissertations (Comprehensive)

Human Uncoupling Protein 2 (hUCP2) is one of five known human UCPs which are found in the inner mitochondrial membrane and have been shown to facilitate the translocation of protons from the intermembrane space to the mitochondrial matrix. The detailed physiological role of UCP2 proton transport, the mechanism by which it mediates this proton transport, as well as its structure has also yet to be elucidated. In order to help determine the topology of UCP2 embedded in the membrane as well as its mechanism of proton transport, the intrinsic fluorescence properties of the two tryptophan residues (Trp) present in its …

Lipid Raft Formation And Peptide-Lipid Interactions In Myelin Model Membranes, Ashtina R. Appadu

Theses and Dissertations (Comprehensive)

Multiple sclerosis (MS), a demyelinating disease affecting 75,000 Canadians and almost 400,000 Americans, is one of the most prevalent diseases in young adults. Unfortunately, there exist no known cures to date and the pathways involved in the progression of the disease remain relatively obscure. The demyelination process triggered by the onset of MS, affects the lipid composition of the myelin membrane and causes a loss in viable myelin which can in turn greatly impact the proper functioning of the central nervous system (CNS). The cholesterol content of myelin fluctuates during MS and consequently this could affect the fluidity as well …

Conformation And Ion Transport Of Neuronal Uncoupling Proteins: Ucp2, Ucp4, And Ucp5, Tuan Hoang

Theses and Dissertations (Comprehensive)

Located in the inner mitochondrial membrane of brown adipose tissue, uncoupling protein -1 (UCP1) dissipates the proton electrochemical gradient, causing reduction in the rate of ATP synthesis, and generates heat by non-shivering thermogenesis. Three other UCP homologs (UCP2, UCP4 and UCP5), expressed in neurons, are suggested to have potential roles in the function and protection of the central nervous system (CNS). Up to date, structural information for UCPs still remains limited. Extensive biochemical studies on UCP2 have provided adequate evidence for its participation in proton and anion transport. So far, no functional studies in proteoliposome systems have been performed on …