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Medicinal-Pharmaceutical Chemistry Commons

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Full-Text Articles in Medicinal-Pharmaceutical Chemistry

Development Of Diverse Size And Shape Rna Nanoparticles And Investigation Of Their Physicochemical Properties For Optimized Drug Delivery, Daniel L. Jasinski Jan 2017

Development Of Diverse Size And Shape Rna Nanoparticles And Investigation Of Their Physicochemical Properties For Optimized Drug Delivery, Daniel L. Jasinski

Theses and Dissertations--Pharmacy

RNA nanotechnology is an emerging field that holds great promise for advancing drug delivery and materials science. Recently, RNA nanoparticles have seen increased use as an in vivo delivery system. RNA was once thought to have little potential for in vivo use due to biological and thermodynamic stability issues. However, these issues have been solved by: (1) Finding of a thermodynamically stable three-way junction (3WJ) motif; (2) Chemical modifications to RNA confer enzymatic stability in vivo; and (3) the finding that RNA nanoparticles exhibit low immunogenicity in vivo.

In vivo biodistribution and pharmacokinetics are affected by the physicochemical properties, such ...


Towards An Understanding Of Pharmacologically Induced Intracellular Changes In Nicotinic Acetylcholine Receptors: A Fluorescence Microscopy Approach, Ashley M. Loe Jan 2016

Towards An Understanding Of Pharmacologically Induced Intracellular Changes In Nicotinic Acetylcholine Receptors: A Fluorescence Microscopy Approach, Ashley M. Loe

Theses and Dissertations--Chemistry

Upregulation of nicotinic acetylcholine receptors (nAChRs) is a well-documented response to chronic nicotine exposure. Nicotinic acetylcholine receptors are pentameric ligand-gated ion channels consisting of alpha (α2-10) and beta (β2-4) subunits. Nicotine, an agonist of nAChRs, alters trafficking and assembly of some subtypes of nAChRs, leading to an increase in expression of high sensitivity receptors on the plasma membrane. These physiological changes in nAChRs are believed to contribute to nicotine addiction, although the mechanism of these processes has not been resolved. Recently, many studies have converged on the idea that nicotine induces upregulation by an intracellular mechanism. In this dissertation, expression ...


Design, Synthesis, And Pharmacological Evaluation Of Three Series Of Lobelane Analogs As Inhibitors Of The Vesicular Monoamine Transporter (Vmat2), John P. Culver Jan 2015

Design, Synthesis, And Pharmacological Evaluation Of Three Series Of Lobelane Analogs As Inhibitors Of The Vesicular Monoamine Transporter (Vmat2), John P. Culver

Theses and Dissertations--Pharmacy

Methamphetamine (METH) abuse is a serious problem in the United States and worldwide. The reward experienced by METH users is due to the increase in extracellular dopamine (DA) concentrations caused by an interaction between METH and the DA transporter (DAT) as well as the Vesicular Monoamine Transporter-2 (VMAT2). The reward felt by users of METH leads to further use of the drug and subsequent abuse. The current project examined the ability of three novel series of lobelane analogs to interact with a binding site on the Vesicular Monoamine Transporter-2 (VMAT2) in an attempt to inhibit the effects of METH. Lobelane ...


Quantification Of Factors Governing Drug Release Kinetics From Nanoparticles: A Combined Experimental And Mechanistic Modeling Approach, Kyle Daniel Fugit Jan 2014

Quantification Of Factors Governing Drug Release Kinetics From Nanoparticles: A Combined Experimental And Mechanistic Modeling Approach, Kyle Daniel Fugit

Theses and Dissertations--Pharmacy

Advancements in nanoparticle drug delivery of anticancer agents require mathematical models capable of predicting in vivo formulation performance from in vitro characterization studies. Such models must identify and incorporate the physicochemical properties of the therapeutic agent and nanoparticle driving in vivo drug release. This work identifies these factors for two nanoparticle formulations of anticancer agents using an approach which develops mechanistic mathematical models in conjunction with experimental studies.

A non-sink ultrafiltration method was developed to monitor liposomal release kinetics of the anticancer agent topotecan. Mathematical modeling allowed simultaneous determination of drug permeability and interfacial binding to the bilayer from release ...


Amalgamation Of Nucleosides And Amino Acids In Antibiotic Biosynthesis, Sandra H. Barnard Jan 2013

Amalgamation Of Nucleosides And Amino Acids In Antibiotic Biosynthesis, Sandra H. Barnard

Theses and Dissertations--Pharmacy

The rapid increase in antibiotic resistance demands the identification of novel antibiotics with novel targets. One potential antibacterial target is the biosynthesis of peptidoglycan cell wall, which is both ubiquitous and necessary for bacterial survival. Both the caprazamycin-related compounds A-90289 and muraminomicin, as well as the capuramycin-related compounds A-503083 and A-102395 are potent inhibitors of the translocase I enzyme, one of the key enzymes required for cell wall biosynthesis. The caprazamycin-related compounds contain a core nonproteinogen b-hydroxy-a-amino acid referred to as 5’-C-glycyluridine (GlyU). Residing within the biosynthetic gene clusters of the aforementioned compounds is a shared open reading ...


Development Of Novel Chemical Tools For Proteasome Biology & A New Approach To 1-Azaspirocyclic Ring System, Lalit Kumar Jan 2012

Development Of Novel Chemical Tools For Proteasome Biology & A New Approach To 1-Azaspirocyclic Ring System, Lalit Kumar

Theses and Dissertations--Chemistry

The proteasome, a multiprotease complex, is clinically validated as an anticancer target by the FDA approval of bortezomib and carfilzomib for the treatment of multiple myeloma. The emergence of resistance to proteasome inhibitors however remains a major clinical challenge. Recently, distinct types of proteasomes termed ‘intermediate proteasomes’, which contain unconventional mixtures of catalytic subunits, have been implicated with drug resistance of tumor cells. In elucidating the role of intermediate proteasomes in drug resistance, a crucial step is to unequivocally determine the subunit composition of intermediate proteasomes in cells. With this in mind, the goal of the studies reported in this ...