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β-peptides are an attractive alternative to peptides as therapeutics owing to increased serum half-lives and resistance to in vivo degradation. This research involves the study of biologically active beta peptides targeting Gai3, a member of the G-protein signaling family. G-protein signaling is initiated and modulated by binding of ligands called guanine nucleotide exchange factors (GEFs). When GEFs bind to Gai3, it enhances Akt activity and cell migration, thus implicating it in wound healing, tumor cell migration, neuronal development, and endothelial cell migration. A GDP-selective GTPase binding peptide, KB-752 has previously been demonstrated to enhance spontaneous activity of Gai3. The KB752- Gαi3 interaction relies heavily on three key residents (Glu, Phe, Trp). The current research focuses on the design and synthesis of β3-peptides that can mimic the activity of KB-752 and thereby bind to GTPase (Gαi3). After testing the GTPase activity of CDC42 and RhoA with the peptides, it was concluded that the peptides do not have notable binding specificity to GTPase CDC42 and RhoA.
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Ding, Kexin, "Design of Gαi3 binding β3 peptides as potential anti-metastatic reagents" (2015). Senior Projects Fall 2015. 14.