Nicole Conte, Boyes Lab & Danielle Gomes Rodrigues, Meisel Lab, Graduate Students, GW Department of Chemistry
The Department of Chemistry Presents, via Online and In-person Presentation: Nicole Conte, Boyes Lab & Danielle Gomes Rodrigues, Meisel Lab, Graduate Students, GW Department of Chemistry
Fri, 29 April, 20222:00pm - 3:00pm
Nicole Conte, Graduate Student, Boyes Lab, GW Department of Chemistry
Aromatic polyamide brushes for anti-antifouling and anti-microbial surfaces
Surface biofouling is a nuisance and a hazard in industries such as marine transport and health care. Marine biofouling leads to costly maintenance and slowing of transport. Whereas, biofouling in medical environments is a leading cause of secondary infection. Anti-fouling and anti-microbial polymer coatings have been used to reduce the impact of each of these issues. However, traditional coatings fall short in terms of durability and longevity. Recently, there has been an increasing focus on the use of polymer brushes as anti-fouling coatings due to their well-defined structure and functionality and the ability to covalently attach brushes to a range of different surfaces. Despite these benefits, traditional polymer brushes still suffer from degradation over time due to the structure of the vinyl monomers typically used for their synthesis. The recent discovery of chain growth condensation polymerization allows for the synthesis of durable rigid rod aromatic polyamide brushes with the potential to combat the stability problems of traditional random coil brush coatings. It has been shown by a previous group member that the addition of a poly(ethylene glycol)(PEG) side chain to rigid rod aromatic polyamide brushes reduces surface fouling and does so in a superior manner to existing PEG coatings. However, the fundamental reason behind the superior performance of these systems have not been explored, nor have their structure-property relationships. By altering the length and location of the PEG functional groups on aromatic polyamide brushes, we hope to better understand and optimize the factors that influence their performance as an anti-fouling coating. Furthermore, zwitterion-containing polymers have also been shown to have excellent anti-fouling and anti-microbial properties in random coil brush systems. In future work, we plan to further expand the current capabilities of our aromatic polyamide brush systems by introducing zwitterion functionality to polymers.
Bio
Nicole received her BS in chemistry from Emmanuel College in Boston, MA. In the Spring of 2020, she joined the Boyes lab at GWU. Her current research focuses on functionalization of aromatic polyamides for anti-fouling and anti-microbial surfaces.
Danielle Gomes Rodrigues, Graduate Student, Meisel Lab, GW Department of Chemistry
Conformational Changes in Amino Acid Based Heterofunctionalized Concave Scaffolds for Protein Surface Recognition
The term “undruggable” has been used to describe the ~75% of the human proteome that lacks deep, hydrophobic pockets to which small molecule can bind. With limited chemical tools to study these challenging targets, many proteins that participate in disease progression remain understudied and undrugged. To address this issue, we have synthesized concave scaffolds to target protein surface and expand the druggable proteome. A cyclic tetramer of 2,4-dialkoxy-meta-aminomethylbenzoic acid (Mmb) was shown to afford a cavity resulting from bifurcated hydrogen bonds and flexible sp3carbons in the backbone. A library of macrocycles with the general structure cyc(Mmb-Xaa-Xaa-Mmb-Xaa-Xaa), where Xaa is any alpha amino acid, was prepared to investigate how heterogeneous backbones affect macrocyclic conformation and cavity formation. The macrocycles were obtained by synthesizing a linear peptide chain via solid-phase peptide synthesis followed by macrocyclization in solution. Nuclear Magnetic Resonance and Circular Dichroism techniques are used to compare macrocycle conformations in solution while X-ray crystallography is used to assess solid phase structure. Recently, a series of cyc(Mmb-Ala-Ala-Mmb-Ala-Ala) macrocycles of varying α-carbon chirality and functionalization at the alkoxy positions of Mmb show that macrocycle folding is dictated by the chirality of the backbone. Preliminary studies suggest that while chirality is a major structural determinant, scaffold conformation is largely unperturbed by varying MAMBA and amino acid side chains. In addition, the introduction of positively charged residues to yield cyc(Mmb-Ala-Lys-Mmb-Ala-Lys) shows progress towards water solubility and bioavailability.
Bio
Dani moved from Campinas, her hometown in Brazil, to Connecticut for her junior year of High School. She had her first lab experience in AP Chemistry and was immediately hooked. Her studies continued at Hamilton College (Clinton, NY), resulting in a B.A. in Biochemistry/Molecular Biology and French/Francophone Studies in 2019. She started her graduate career at the University of Connecticut and moved to The George Washington University in January 2020. She joined the Meisel Lab later that year and has been working on the synthesis of peptide-based concave scaffolds to target protein surfaces and expand the druggable proteome.
