Edit Y. Tshuva

Phenolato Ti(iv) hexacoordinate complexes for anticancer chemotherapy: enhancement of solubility, hydrolytic stability, and cytotoxicity

Five titanium(iv) phenolato complexes were synthesized and fully characterized, and they showed high cytotoxicity, high hydrolytic stability, and enhanced solubility. The halogenated derivatives are identified as the most promising drug candidates.

Hydrolytically Stable and Cytotoxic [ONON]2Ti(IV)-Type Octahedral Complexes

A new family of titanium(IV) complexes based on [ONON] diaminobis(phenolato) ligands with Me, Br, Cl, and F ortho substitutions was synthesized and characterized. X-ray structures of three derivatives revealed homoleptic L

Targeting Protein Interaction Hotspots Using Structured and Disordered Chimeric Peptide Inhibitors

The main challenge in inhibiting protein-protein interactions (PPI) for therapeutic purposes is designing molecules that bind specifically to the interaction hotspots. Adding to the complexity, such hotspots can be within both structured and disordered interaction interfaces. To address this, we present a strategy for inhibiting the structured and disordered hotspots of interactions using chimeric peptides that contain both structured and disordered parts. The chimeric peptides we developed are comprised of a cyclic structured part and a disordered part, which target both disordered and structured hotspots. We demonstrate our approach by developing peptide inhibitors for the interactions of the antiapoptotic iASPP protein. First, we developed a structured, α-helical stapled peptide inhibitor, derived from the N-terminal domain of MDM2. The peptide bound two hotspots on iASPP at the low micromolar range and had a cytotoxic effect on A2780 cancer cells with a half-maximal inhibitory concentration (IC