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Full-Text Articles in Analytical Chemistry
Rotational Tuning Of Transmembrane Helix Properties Based On The Precise Placements Of Aromatic And Charged Residues, Matthew J. Mckay
Rotational Tuning Of Transmembrane Helix Properties Based On The Precise Placements Of Aromatic And Charged Residues, Matthew J. Mckay
Graduate Theses and Dissertations
Designed model transmembrane peptides and oriented 2H and 15N solid-state nuclear magnetic resonance (NMR) spectroscopy were used to analyze how simple sequence modifications can influence peptide structure, behavior and dynamics as well as for determining the pKa of glutamic acid at the membrane interface. The GW5,19ALP23 (acetyl-GGALW(LA)6LWLAGA-amide) peptide framework adopts a well-defined tilted orientation in lipid bilayers (DLPC, DMPC and DOPC) and undergoes low amounts of dynamic motion. The sequence was initially modified by moving the Trp residues outwards to positions 4 and 20. This new sequence GW4,20ALP23 (acetyl-GGAW(AL)7AWAGA-amide) displays high amounts of signal averaging of NMR observables caused by …
Characterization Of Β-2-Microglobulin Pre-Amyloid Oligomers And Their Role In Amyloid Inhibition, Tyler M. Marcinko
Characterization Of Β-2-Microglobulin Pre-Amyloid Oligomers And Their Role In Amyloid Inhibition, Tyler M. Marcinko
Doctoral Dissertations
In dialysis patients, β-2 microglobulin (β2m) can aggregate and eventually form amyloid fibrils in a condition known as dialysis-related amyloidosis, which deleteriously affects joint, bone, and organ function, and eventually causes organ failure. To understand the early stages of the amyloid assembly process, we have employed a series of biophysical tools including chromatography, spectroscopy, and most especially, native electrospray ionization (ESI) together with ion mobility mass spectrometry (IM-MS) to study soluble pre-amyloid oligomeric species. We have also collaborated and integrated computational modeling to help better understand and rationalize the structural basis behind oligomerization. Recently, several small molecules have been identified …
Bisthioether Stapled Peptides Targeting Polycomb Repressive Complex 2 Gene Repression, Gan Zhang
Bisthioether Stapled Peptides Targeting Polycomb Repressive Complex 2 Gene Repression, Gan Zhang
Dissertations, Theses, and Capstone Projects
Interactions between proteins play a key role in nearly all cellular process, and therefore, disruption of such interactions may lead to many different types of cellular dysfunctions. Hence, pathologic protein-protein interactions (PPIs) constitute highly attractive drug targets and hold great potential for developing novel therapeutic agents for the treatment of incurable human diseases. Unfortunately, the identification of PPI inhibitors is an extremely challenging task, since traditionally used small molecule ligands are mostly unable to cover and anchor on the extensive flat surfaces that define those binary protein complexes. In contrast, large biomolecules such as proteins or peptides are ideal fits …