R18 TFA is a peptide antagonist of 14-3-3, with KD of 70-90nM [1]. R18 TFA can inhibit all members of the 14-3-3 protein family with a very similar affinity coefficient, and effectively utilize the amphiphilicity of the 14-3-3 binding channel to competitively inhibit phosphorylation and non-14-3-3-dependent protein-protein interactions [2]. Disruption of 14-3-3 via the R18 TFA switches nerve growth factor- and myelin-associated glycoprotein-dependent repulsion to attraction in rat DRG neurons [3]. The R18 TFA has been widely used to disrupt the binding of 14-3-3 to the ligands, thereby screening out the proteins that are regulated by 14-3-3[4].
In vitro, R18 TFA treatment at 8μM for 48 hours significantly inhibited the viability of MMQ cells and reduced the expression of 14-3-3η[5].
References:
[1] Wang B, Yang H, Liu Y C, et al. Isolation of high-affinity peptide antagonists of 14-3-3 proteins by phage display[J]. Biochemistry, 1999, 38(38): 12499-12504.
[2] Liu J, Cao S, Ding G, et al. The role of 14‐3‐3 proteins in cell signalling pathways and virus infection[J]. Journal of cellular and molecular medicine, 2021, 25(9): 4173-4182.
[3] Kent C B, Shimada T, Ferraro G B, et al. 14-3-3 proteins regulate protein kinase a activity to modulate growth cone turning responses[J]. Journal of Neuroscience, 2010, 30(42): 14059-14067.
[4] Repton C, Cullen C F, Costa M F A, et al. The phospho-docking protein 14-3-3 regulates microtubule-associated proteins in oocytes including the chromosomal passenger Borealin[J]. PLoS Genetics, 2022, 18(6): e1009995.
[5] Zhao S, Li B, Li C, et al. The apoptosis regulator 14-3-3η and its potential as a therapeutic target in pituitary oncocytoma[J]. Frontiers in endocrinology, 2019, 10: 797.