Abstract:
Targeted drug delivery systems for cancer therapy are rapidly advancing, but the availability of efficient targeting ligands remains limited. This project focuses on chlorotoxin, a 36-amino-acid peptide derived from the scorpion Leiurus quinquestriatus, stabilized by four disulfide bonds. Chlorotoxin selectively binds to cancer-associated targets such as MMP-2, Annexin-2, and calcium-activated chloride ion channels, showing high specificity toward glioma cells. In this work, chlorotoxin was engineered for applications in photodynamic therapy, PROTAC development, and Gallium-68 chelation for radioisotopic imaging of gliomas. The second project addresses antimicrobial resistance (AMR), a major global health challenge driving the need for new therapeutics. This work focuses on thanatin, a 21-amino-acid β-hairpin antimicrobial peptide active against both Gram-positive and Gram-negative bacteria. To improve its proteolytic stability, selected residues were modified using non-canonical amino acids such as 2-aminoisobutyric acid (Aib) and a β-oxy-δ-threonine dipeptide mimetic. These modifications were designed to preserve the peptide’s β-hairpin structure and antimicrobial activity while enhancing stability, contributing to the development of next-generation antimicrobial therapeutics.
