Physical Sciences

Parsons, Travis; Lippert, Peter; Bartley, John (University of Utah)
Faculty Advisor: Lippert, Peter (University of Utah - College of Mines and Earth Science, Geology & Geophysics); Bartley, John (University of Utah - College of Mines and Earth Science, Geology & Geophysics)

Field observations and geochronological measurements of plutons in Yosemite Valley suggest that plutons grow incrementally as a series of stacked sheets of smaller intrusions (i.e., dikes and sills) (Coleman et al., 2004; Glazner et al., 2004; Bartley et al., 2006). This interpretation is in contrast to the traditional view of pluton emplacement through crystallization of a single, massive magma chamber. Most of the observations supporting incremental pluton emplacement use the relationship between zircon U-Pb dating of pluton sections and estimated granitic magma cooling rates to argue that a single magmatic event would crystallize significantly faster than the geochronologic data permit. Incremental pluton emplacement also predicts specific relationships between the age of intruded sheets of magma and the original orientation of these sheets, such that older sheets are expected to be tilted or deformed more than younger sheets. Here we test this prediction of differential tilting by measuring the paleomagnetic inclination preserved in well-dated and structurally characterized sheets of the Tuolumne Intrusive Suite. Magnetic inclination provides a tilt-meter with respect to the Earth's magnetic field direction at the time of pluton emplacement; the reference inclination assuming an untitled pluton is known from independent data sets. We also present rock magnetic data (temperature-dependent magnetic susceptibility, magnetic remanence characteristics) and results from petrographic investigations to characterize the mineralogy and stability of the magnetization. Our results suggest that the low-titanium magnetite remanence carriers are primary and are not biased by secondary magnetizations. The distribution of magnetic inclinations in our sample set — in which older sheets on the periphery of the pluton are shallower than those in younger, more interior sheets, and with respect to the reference inclination — is consistent with predictions from the incremental pluton emplacement hypothesis.

Keyes, E. Dalles; Alvey, Brighton; Smith, T. Andrew; Roberts, Andrew G. (University of Utah)
Faculty Advisor: Roberts, Andrew G. (University of Utah, Chemistry)

Medicinal chemistry has long relied on the development of small molecule therapeutics to treat human disease. Small molecules affect change at the cellular level through specific interactions with biological targets (e.g. proteins), thereby eliciting a desired physiological response. Conversely, small molecules can also interact non-specifically, which can complicate their targeted application. In many cases, the use of peptide-based medicines can address this limitation. Like small molecules, peptide-therapeutics are designed to modulate specific biological processes. They often exhibit desirable activity at low concentrations as a result of high selectivity. Being comprised of natural amino acid building blocks, peptides offer an inherent advantage. Their natural breakdown leads to minimally toxic degradation products. However, premature and rapid degradation can result in failure to reach an established target in vivo. The cyclization of peptides has shown to be a promising strategy to address this problem. Inspired by Nature's wide collection of non-ribosomal peptides, specifically those comprising electron-rich aromatic moieties, we have developed a new chemical strategy for the synthesis of cyclic peptides. Our cyclization method leverages the inherent reactivity of the tyrosine (Tyr) phenol nucleus with electrophilic 1,2,4-triazoline-3,5-dione (TAD) moieties. Using this reaction, we can construct macrocyclic peptidomimetic scaffolds. Upon synthesizing an N4-substituted 1,2,4-triazolidine-3,5-dione (aka urazole) at the N-terminus of a solid-supported peptide, the urazole moiety is chemoselectively oxidized under mild conditions to generate a TAD derivative in situ. The TAD moiety reacts with the sidechain phenol nucleus of internally or terminally located Tyr residues and results in the formation of a macrocyclic peptide. We envision that this method will significantly augment current strategies for constructing macrocyclic peptides by enabling the facile synthesis of complex peptidomimetic scaffolds. Furthermore, this approach is anticipated to expand the repertoire of tools used for developing medicinally relevant peptides and, thus, may be suitable for preparing unique peptide-based therapeutics.