Structure-Guided SOCS3 Peptidomimetics: Design and Functional Characterization

∼ 10 μM) in comparison to the affinity of the isolated regions. This was determined by means of MicroScale Thermophoresis (MST). Circular dichroism (CD) and fluorescence spectroscopy demonstrated that turn-inducing motifs stabilize native-like conformations, correlating with enhanced serum stability. To preliminarily evaluate potential cellular effects, we assessed their serum stabilities and their cytotoxicity in MDA-MB-231 and MDA-MB-468 cells once conjugated to a small Cell-Penetreting Peptide (CPP). In both cases, the good biocompatibility of the designed mimetics appeared promising for evaluating signaling-dependent effects. These findings validate a multiregion, structure-guided design strategy and identify an improved SOCS3 proteomimetic scaffold with potential for targeting dysregulated JAK/STAT signaling in cancer.