Molecular Biology Commons^™

One-Pot Heteroconjugate Addition-Diels-Alder Reactions And Acetate-Catalyzed Aldol Reactions Of Α-Silyl Nitriles, Carly Mueller

Honors Theses

1. A one-pot three-step Diels–Alder reaction sequence of ethyl propiolate and thiols can be performed to produce high yields of complex bicyclic products. A KOt-Bu-catalyzed thioconjugate addition of thiols to enoates, oxidation of the generated thioenoate by mCPBA, and Li-catalyzed Diels–Alder addition of cyclopentadiene occur in situ, without any purification of intermediates.
2. Stereoselectivity of the Diels–Alder product was examined by utilizing a chiral sulfone substrate. It was determined that these substrates were unable to provide significant stereochemical control.
3. Silylation of 3-phenylpropionitrile is achieved at the α-position with trimethylsilyl trifluoromethanesulfonate and trialkylamine base. Catalyzed by tetrabutylammonium acetate (2.5 mol%), …

Do The Inter-Nucleotide Domain Loops Act As An Entropic Sink In The Catalytic Activity Of 3-Phosphoglycerate Dehydrogenase (3pgdh)?, Cristina Adelia Meeham

Honors Theses

In protein science the relationship between protein dynamics and catalytic activity are the subject of considerable contemporary interest. Although protein motions are frequently observed during ligand binding and release steps, the contribution of protein motions to the catalysis of bond making/breaking processes is more difficult to probe and verify. Currently, the field of protein science is trying to uncover the deeper role that dynamics plays in the catalytic activity and allosteric regulation of proteins and to better understand how to more effectively and efficiently target proteins in cancer therapeutics and other metabolic pathways.

Adenovirus Type 5 Virions Asymmetrically Lose Icosahedral Structure At Low Phs Of Endosomes, Jennifer Marie Jarboe

Honors Theses

After receptor mediated endocytosis into an endosome, human Adenovirus Type 5 (Ad5) undergoes structural changes that allow the virus to release a viral protein, pVI, that lyses the endosome and releases the virus core into the cytosol, where it travels to the nucleus to insert its genome. Structural studies of Ad5 at a range of pHs typical of endosomes (7.5-4.5) using a transmission electron microscope show that Ad5 undergoes asymmetrical loss of proteins from vertex regions at the pH of the late endosome (pH5.15). Following further acidification, Ad5 ejects core material preferentially through one vertex—indicating an asymmetry at one vertex …

The Inner Workings Of The Dna Copying Nanomachine : Kinetic Studies Of Dna Polymerase I From The Thermophilic Bacterium Rhodothermus Marinus, Emily P. Kornberg

Honors Theses

DNA polymerase I from Rhodothermus marinus is a high-fidelity DNA polymerase capable of operating at high temperatures and incorporating 2´,3´-dideoxynucleotides. The R. marinus DNA Polymerase I active site contains an unusual proline in the middle of a mobile “O helix.” This proline residue is hypothesized to decrease the relative free energy of a kinetic checkpoint termed the ajar conformation, and thereby slow the incorporation of incorrect nucleotides. We aim to test the accuracy of a newly developed nucleotide incorporation model, in which the enzyme allows the template to interact with the bound dNTP in the ajar conformation, whether correct or …

Trimethylsilyl Trifluoromethanesulfonate-Mediated Additions To Acetals, Nitrones, And Aminals, Chelsea Safran

Honors Theses

One-pot reactions were studied in order to develop procedures for the formation of important carbon-carbon and carbon-nitrogen bonds that are easily reproducible. In the presence of trimethylsilyl triflouromethanesulfonate (TMSOTf), Mukaiyama-aldol and aldol-like reactions occur in one-pot due to TMSOTf acting as a Lewis acid and silylating agent. A variety of reactions, including methoxyalkylation, were performed to form carbon-nitrogen bonds. Here, research involving TMSOTf-mediated additions to acetals, nitrones, and aminals will be discussed.

The Relationship Between Live Coral And Macroalgae In South Caicos As Influenced By Herbivorous Fishes, Sarah Byce

Honors Theses

Marine life is the basis for most industries in the Turks and Caicos Islands, located on the outskirts of the Caribbean Sea. Few studies have been carried out to assess the current status of reefs in this region, especially those off the shore of South Caicos Island. The AGRRA v.4.0 methodologies were employed create baseline assessments of stony corals, macroalgae and associated fishes and to explore the relationships between these key reef organisms. This study was based on 10 different locations both inside and outside of Marine Protected Areas (MPAs) and including exposed and sheltered reefs in proximity to South …

Elucidation Of The Pax/Six Gene Regulatory Network In Ephydatia Muelleri, Anna Rued

Honors Theses

The evolution of gene regulatory networks accounts for much of the diversity we observe in the animal kingdom. In particular, the Pax/Six/Eya/Dac gene network has been known to play critical roles in development of all bilaterians and cnidarians. However, this network has not been characterized in Porifera. These studies focus on tracing the evolutionary history of the PSED network back to the most basal organism in the metazoan phylogeny through demonstrating the presence of a direct gene regulatory network between PaxB and Six1/2 orthologs in sponges. To this end, putatitve Six1/2 cis- regulatory elements were identified while the PaxBprd transcription …

The Optimization Of A One-Pot Heteroconjugate Addition-Oxidation-Diels-Alder Reaction, Christina Vivelo

Honors Theses

Ynoate esters are ideal reagents for one-pot reactions due to their ability to undergo multiple addition reactions in one flask. Ethyl propiolate undergoes a heteroconjugate addition reaction with aromatic thiol nucleophiles, producing an enoate which is then oxidized by m-CPBA and is able to undergo a Diels–Alder reaction with cyclopentadiene. The work presents the optimization of a three-step heteroconjugate addition-oxidation-Diels–Alder reaction to yield cyclic compounds favoring endo stereochemistry, which may be used in further synthesis of biologically active compounds such as (+)-Methyl-5-epi-Shikimate or Deipeptyl-IV-Peptidase inhibitor.

The Role Of Histidines In Neurosteroid Binding Of Nmda Glun2b And D Subunits, Sarah Rhoads

Honors Theses

Implicit in cellular mechanisms essential for learning and memory, NMDA receptors are heterotetrameric members of the family of ionotropic glutamate receptors. Activation of the glutamate-specific receptor subunits results in the opening of ion channels, triggering an excitatory pathway, which can be moderated by certain endogenous and exogenous compounds. Previous research with the endogenous neurosteroids pregnenolone sulfate (PS) and 3α-hydroxy-5-β-20-one sulfate (PregS) have indicated that the binding of these neurosteroids to NMDA receptors containing the four A-D isoforms of the GluN2 subunit affects current flow through them1. Binding of PS to NMDA receptors containing GluN2A or GluN2B subunits causes an increased …

Determination Of The Atomic Resolution Structure Of A Dna Polymerase I Isolated From Rhodothermus Marinus, Natalie S. Omattage

Honors Theses

DNA polymerase I employs a multistep mechanism for sorting correctly paired nucleotides from mismatches. We aim to characterize reaction intermediates during nucleotide selection to better understand how this class of enzymes achieves high DNA replication fidelity. DNA polymerase I from R. marinus contains an unusual and disruptive proline in the mobile O helix near the active site. To characterize this enzyme, the structure of the large (5´-to-3´ exo-deficient) fragment of the R. marinus DNA polymerase I (RF) was solved to 2.95 Å (R = 0.234) using multi-wavelength anomalous dispersion. Alignment …

A Comparison Of The Low Mode And Monte Carlo Conformational Search Methods, Carol A. Parish, Rosina Lombardi, Kent Sinclair, Emelyn Smith, Alla Goldberg, Melissa Rappleye, Myrianne Dure

Chemistry Faculty Publications

The Low Mode (LM) and Monte Carlo (MC) conformational search methods were compared on three diverse molecular systems; (4R, 5S, 6S, 7R)-hexahydro-5,6-dihydroxy-1,3,4,7-tetrakis(phenylmethyl)-2H-1,3-diazapin-2-one (1), 2-methoxy-2-phenyl-2-triflouromethyl-N-α-methyl benzyl propanamide (2) and a trimeric 39-membered polyazamacrolide (3). We find that either method, or a combination of the methods, is equally efficient at searching the conformational space of the smaller molecular systems while a 50:50 hybrid of Low Mode and Monte Carlo is most efficient at searching the space of the larger molecular system.

Morfología Y Moléculas: Bases Complementarias De La Sistemática Moderna, Rafael O. De Sá, David M. Hillis

Biology Faculty Publications

RESUMEN

El auge de las técnicas moleculares en las últimas dos décadas ha traído nuevos enfoques en los estudios sistemáticos. Aquí presentaremos una revisión del uso, las aplicaciones, y los problemas de las principales metodologías de trabajo. Cada una de estas técnicas es aplicable a algunos problemas e inapropiada para otros, y es importante entender las suposiciones y limitaciones de cada técnica. Concluimos que el uso combinado de los enfoques morfológicos y moleculares otorga mejor resolución a los problemas sistemáticos.

ABSTRACT

The development of molecular techniques during the last two decades has brought new approaches to the analysis of systematic …