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Medicinal-Pharmaceutical Chemistry Commons

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Articles 1 - 9 of 9

Full-Text Articles in Medicinal-Pharmaceutical Chemistry

Poly(Ethyl Glyoxylate) Solid-Core Particles For Drug Delivery, Michael Thomas Gambles Aug 2017

Poly(Ethyl Glyoxylate) Solid-Core Particles For Drug Delivery, Michael Thomas Gambles

Electronic Thesis and Dissertation Repository

The ability to trigger the degradation of polymeric nanoparticles (NPs) by a specific stimulus can provide a method of improved drug targeting and selective release capabilities in vivo. The challenge for most polymeric drug delivery systems remains the necessity for many stimuli events to trigger the release of cargo. Polymeric nanotechnology containing “self-immolative polymers” looks to alleviate the reliance on high concentrations of stimuli by undergoing complete end-to-end depolymerization via a single stimulus-mediated reaction of an end-cap. Herein, NPs were developed using poly(ethyl glyoxylate) (PEtG) blended with poly(d,l-lactic acid) (PLA) to encapsulate a hydrophobic cargo to be ...


Crystal Engineering Of Active Pharmaceutical Ingredients With Low Aqueous Solubility And Bioavailability, Jenna M. Skieneh Aug 2017

Crystal Engineering Of Active Pharmaceutical Ingredients With Low Aqueous Solubility And Bioavailability, Jenna M. Skieneh

Electronic Thesis and Dissertation Repository

Approximately 75% of new molecular entities approved by the Food and Drug Administration (FDA) for use in the pharmaceutical industry are found to have poor aqueous solubility. This undesirable attribute leads to consequences such as higher doses required to reach therapeutic levels, greater vulnerability to food effects, lesser fraction absorbed in the small intestine and damage to the environment due to increased quantity of excretion. The addition of an excipient (i.e. a FDA approved inactive ingredient) to the molecular structure of an active pharmaceutical ingredient (API) through intermolecular bonding is of growing interest because the properties of the API ...


The Design And Synthesis Of Ghrelin Analogues As Non‐Invasive Ghs‐R1a Imaging Probes, Carlie L. Charlton Feb 2016

The Design And Synthesis Of Ghrelin Analogues As Non‐Invasive Ghs‐R1a Imaging Probes, Carlie L. Charlton

Electronic Thesis and Dissertation Repository

The field of molecular imaging is constantly growing and evolving in order to provide the best possible healthcare for patients in various stages of disease and therapy. Molecular imaging aims to locate specific markers of disease by selectively targeting the markers of interest with high selectivity and visualizing the accumulation using external detection. The growth hormone secretagogue receptor-1a (GHS-R1a) has been shown to be involved in various important biological functions such as energy homeostasis and cardiac contractility. GHS-R1a has shown involvement in proliferation, migration and cell invasion of specific cancer subtypes. Therefore, targeting GHS-R1a is an important marker of different ...


Design, Synthesis, And Reactivity Of Bimetallic Complexes Of Dimethylplatinum(Ii) Containing Ditopic Ligands, Matthew S. Mccready Apr 2015

Design, Synthesis, And Reactivity Of Bimetallic Complexes Of Dimethylplatinum(Ii) Containing Ditopic Ligands, Matthew S. Mccready

Electronic Thesis and Dissertation Repository

This thesis describes a study of monometallic and bimetallic dimethylplatinum(II) complexes containing ditopic nitrogen donor ligands. This work details the design and synthesis of side-to-side and cofacial arranged ligands and their respective coordination chemistry. The study of the synthesis, characterization and reaction mechanisms of the various dimethylplatinum(II) complexes is outlined in detail with special emphasis focused on the reactivity of the complexes towards oxidative addition.

The ditopic ligand 6-dppd, 1,4-di(2-pyridyl)-5,6,7,8,9,10-hexahydrocycloocta[d]pyridazine, was observed to coordinate only a single equivalent of a platinum(II) center. The inability to coordinate a ...


Development Of A Gallium-Containing One-Bead One-Compound Peptide Library For The Discovery Of New Molecular Imaging Probes, Fernanda C. Bononi Aug 2014

Development Of A Gallium-Containing One-Bead One-Compound Peptide Library For The Discovery Of New Molecular Imaging Probes, Fernanda C. Bononi

Electronic Thesis and Dissertation Repository

An eight amino acid one-bead one-compound (OBOC) peptide library, containing a gallium-DOTA complex, was developed in an attempt to overcome common issues associated with the later addition of radionuclides to peptide chains of imaging probes. The further addition of a radionuclide often changes the binding properties of a peptide, as it adds bulk, and possibly charges. MALDI (matrix-assisted laser desorption ionization) tandem mass spectrometry was determined to be the method of choice in order to deconvolute gallium-containing peptide sequences. The library obtained was screened against the breast cancer cell lines MDA-MB-231 and MCF-7. Positive beads were isolated and sequences were ...


Peptidomimetic Ghs-R1a Agonists As Pet Imaging Agents For Prostate Cancer, Milan M. Fowkes Apr 2014

Peptidomimetic Ghs-R1a Agonists As Pet Imaging Agents For Prostate Cancer, Milan M. Fowkes

Electronic Thesis and Dissertation Repository

Contemporary diagnostic techniques for prostate cancer (PCa) have a limited ability to distinguish between benign and malignant disease. The ghrelin receptor has a differential expression in normal, benign and cancerous prostatic tissue. Targeting this receptor with 18F-radiolabelled peptidomimetics would enable differentiation between these disease states via PET imaging. A series of 19F-peptidomimetics were synthesized and characterized by HRMS, HPLC and 1 H-NMR spectroscopy in order to test locations for 18F radioisotope insertion. Competitive receptor binding assays using HEK293/GHS-R1a cells were used to evaluate compound binding affinities. This led to the identification of two lead compounds: [1-Nal4,Lys5(4-FB)]G-7039 ...


Carboxylic Acid Functionalized Butyl Rubber: From Synthesis To Applications, Matthew John Mceachran Feb 2013

Carboxylic Acid Functionalized Butyl Rubber: From Synthesis To Applications, Matthew John Mceachran

Electronic Thesis and Dissertation Repository

Butyl Rubber (RB) is a copolymer of isobutylene (IB) with small percentages of isoprene (IP). Typically these IP units serve as sites for the covalent cross-linking of the rubber, but they can also serve as sites to further functionalize RB. These modifications can expand the potential applications of RB. This thesis describes the synthesis of carboxylic acid functionalized RB and some properties and applications of these materials.


The Development Of Organometallic Oboc Peptide Libraries For Use In Molecular Imaging, Dana R. Cruickshank Aug 2012

The Development Of Organometallic Oboc Peptide Libraries For Use In Molecular Imaging, Dana R. Cruickshank

Electronic Thesis and Dissertation Repository

The discovery of peptide-based targeted imaging agents is hindered by the required addition of a radionuclide that can affect the binding properties of the peptide. Screening of peptide libraries is problematic because they do not take into account the presence of the imaging agent. Herein the development of an organometallic OBOC peptide library that contain a rhenium (I) tricarbonyl-based imaging entity surrogate incorporated directly onto the peptide chain, is reported. Additionally, MALDI tandem mass spectrometry is reported as a method to deconvolute organometallic peptides containing four different rhenium (I) tricarbonyl chelates on the N-terminus of octapeptides. Furthermore, an organometallic OBOC ...


Development Of Single And Multimodality Imaging Probes For Pet, Spect And Fluorescence Imaging, Babak Behnam Azad Sep 2011

Development Of Single And Multimodality Imaging Probes For Pet, Spect And Fluorescence Imaging, Babak Behnam Azad

Electronic Thesis and Dissertation Repository

This dissertation is in an integrated format discussing three major projects centered around probe development. In the first project, novel metal-chelated and fluorinated GLP-1 derivatives were prepared all containing D-Ala-8, a modification known to improve resistance towards degradation by dipeptidyl-peptidase IV. The effect of increased distance between DOTA and the peptide chain was investigated using a spacer, in order to reduce steric effects imposed by DOTA. Placement of linker and DOTA moieties were varied within the GLP-1 sequence to test for optimal metal-complex location. Binding affinity of peptide derivatives was determined in vitro with CHO/GLP-1R cell line and shown ...