Research Projects

Crown ethers are model molecules that can coordinate with metal ions, making them potential candidates for developing inhibitors against metalloenzymes and drugs with metal sequestration properties. These peptides have antimicrobial properties and have been studied for their potential as agents against multi-drug-resistant pathogens. However, their crystallization is challenging due to a dynamic equilibrium between multiple conformations. The group reported the first successful crystallization of a crown ether-containing peptide by creating a smaller crown ring for a more rigid conformation. They also studied the potential of these peptides to induce cell death and inhibit a copper-containing enzyme, tyrosinase, which leaches copper from the enzyme's active site. Based on these preliminary studies, the group proposes creating peptides with crown ether side chains with better yields and conformational rigidity. The crown moiety on the L-DOPA backbone will be synthesized using usual methods, and the amino acid residues can be added by a solid phase peptide synthesizer. The peptide chain length and chirality of amino acids will be varied to achieve a specified secondary structure. Non-protein amino acids like Aib will be introduced to get a helical structure and facilitate crystallization. The objective is to screen these peptides against various metal ions and study their binding efficiency. If successful, these peptides could be promising drug candidates against hyperpigmentation-related skin disorders resulting from overexpression of tyrosinase. The binding of these crown peptides to different metal ions can pave the way for developing metal ion sensors and screen their antimicrobial activity, which could help overcome multi-drug-resistant diseases.