Faculty Sponsor(s)
Andrew Baggett
Location
Jereld R. Nicholson Library: Grand Avenue
Subject Area
Chemistry
Description
Actin is a key protein building block of actin microfilaments, which are constructed and deconstructed in response to cellular signaling pathways to regulate cellular processes such as motility, division, and endocytosis. Arp2/3 Complex is a 7-subunit protein complex that is in involved in cellular construction of branched actin networks, functioning by attaching to the side of a pre-existing actin filament and nucleating a daughter branch. Overexpression of Arp2/3 complex has been linked to the ability of certain metastatic cancers to proliferate. This work describes the synthesis and in vitro biochemical testing of several molecules predicted by computational docking to be inhibitors of Arp2/3 Complex, and therefore of potential interest in clinical applications. A bulk actin polymerization assay is used as the key method to determine the potency of inhibitor candidates. Structure-activity relationships derived from these results are also discussed.
Recommended Citation
Andersen, Katherine; Wade, Natalie; DeRocher, Shelby; Collins, Jordan; Pierson, Christina; Cavas, Levent; Cournia, Zoe; Nolen, Brad J.; and Baggett, Andrew W., "In Vitro Determination of Potency of Small Molecule Inhibitors of Arp2/3 Complex" (2019). Linfield University Student Symposium: A Celebration of Scholarship and Creative Achievement. Event. Submission 43.
https://digitalcommons.linfield.edu/symposium/2019/all/43
In Vitro Determination of Potency of Small Molecule Inhibitors of Arp2/3 Complex
Jereld R. Nicholson Library: Grand Avenue
Actin is a key protein building block of actin microfilaments, which are constructed and deconstructed in response to cellular signaling pathways to regulate cellular processes such as motility, division, and endocytosis. Arp2/3 Complex is a 7-subunit protein complex that is in involved in cellular construction of branched actin networks, functioning by attaching to the side of a pre-existing actin filament and nucleating a daughter branch. Overexpression of Arp2/3 complex has been linked to the ability of certain metastatic cancers to proliferate. This work describes the synthesis and in vitro biochemical testing of several molecules predicted by computational docking to be inhibitors of Arp2/3 Complex, and therefore of potential interest in clinical applications. A bulk actin polymerization assay is used as the key method to determine the potency of inhibitor candidates. Structure-activity relationships derived from these results are also discussed.
