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The Morrill Research Group
General Research Focus
The general research focus of our undergraduate research lab is directed at the investigative design, development, and synthesis of novel and potentially useful organic molecules having applications in the biomaterials and pharmaceutical arenas. We make use of computer modeling tools to understand the relationships between molecular structures and properties, be they biological or physicochemical. The results of our simulations are then used in the rational design of candidate materials and compounds. Potentially successful candidates are targeted for synthesis and evaluation. Currently, our efforts are directed at investigating monomers for restorative dental biomaterials, small-molecule chemotherapeutics, and small-molecule antiviral compounds.
Polymeric Dental Restorative Materials
Not only must a polymeric biomaterial be biologically compatible in the environment in which it is placed, but in many cases for such a material to be practically useful it must also be highly reactive toward polymerization in its monomeric form. Phenyl carbamate esters of acrylic acid have been identified for their high reactivity to photoinitiated radical polymerization. Although much good work has been done toward elucidating a mechanism that accounts for such high reactivity, the question still has not been definitively answered. We are currently employing computer modeling in order to develop Quantitative Structure-Property Relationships (QSPRs) that describe the unusually high reactivity of such monomers. We are also conducting reaction modeling in order to probe various modes of reactivity in order to suggest an explanatory and plausible mechanism of radical polymerization.
Small-Molecule Chemotherapeutics
Histone deacetylase (HDAC) inhibitors have been studied extensively due to their ability to induce growth arrest, differentiation, and apoptosis in cancer cells. Through the development of Quantitative Structure-Activity Relationships (QSARs) and docking inhibitor molecules in a model of the active site of HDAC we have identified a potential HDAC inhibitor and are currently undertaking its synthesis for biological evaluation.
Small-Molecule Antiviral Compounds
RNA is an appealing antiviral therapeutic target because it is also involved in gene expression as it mediates the transfer of information from genes to proteins. Furthermore, RNA can form complex tertiary structures and like proteins, folded RNA molecules also feature binding sites. Generally, these binding sites act as places for RNA-RNA or RNA-protein interactions. However, small molecules can be designed to interact with RNA binding sites to interrupt RNA-RNA or RNA-protein interactions. We are in the early stages of the investigation of inhibitors that are believed to bind to domains II and III of the hepatitis C virus (HCV) internal ribosome entry site. We are doing this by developing QSARs that relate molecular structural features to the tendency of investigated inhibitors to diminish HCV activity.
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