Structural study of Lindqvist polyoxovanadate–peptide conjugates

Polyoxometalates (POMs) are inorganic molecular clusters that exhibit significant biological activity against various pathologies, including cancer. Despite their therapeutic potential, the clinical application of POMs is limited by challenges such as low selectivity and toxicity. To overcome these limitations, conjugation with targeting moieties such as biomolecules and peptides has emerged as a promising strategy to enhance their selectivity. Within this context, the use of spacers can reduce intramolecular interactions between the POM surface and targeting molecules, thereby maintaining their accessibility for biological recognition. In this study, the Lindqvist hexavanadate cluster is functionalized with the antagonist peptide demobesin-1 (DB), with or without spacers, to evaluate the impact of this modification on peptide conformation and biological activity. Our findings provide valuable insights into the optimization of POM-based therapeutic agents with improved selectivity and reduced toxicity.