Vejleder: Stefan Vogel
Forudsætninger: KE505 og KE506 skal være bestået.
Projektbeskrivelse
According to the world health organisation, 1 of 6 deaths is caused by cancer, making cancer the second leading cause of deaths on a global scale. Cogoi, S. et al. reported the use of G4-decoy oligonucleotides anchored to nanoparticles to investigate the delivery and bioactivity in pancreatic cancer cells. They demonstrated that delivery by liposomes marked with cell penetrating peptides TAT and R8 is a feasible strategy to deliver cytotoxic compounds into cells.[1] KRAS is mutated in >90% of pancreatic ductal adenocarcinomas (PDAC). As its inactivation leads to tumor regression, mutant KRAS is considered an attractive target for anticancer drugs. The synthesis and use of lipidated peptides was key to the successful delivery of therapeutic oligonucleotides.
Figure 1. A) Schematic illustration of key components for G4-decoy ON delivery systems 85 nm sized POPC liposomes with membrane anchored G4-ON and a cell-penetrating peptide (TAT) attached (A) and the proposed structure for the G4-forming ONs with P indicating the position of quadruplex-stabilizing para-TINA (P) units (B) Microwave assisted Peptide Synthesizer (Liberty Blue).
Methods: We look forward to students interested to apply methods in automated peptide synthesis such as microwave assisted peptide formation for accelerated synthesis of peptides. This project is designed for students interested to learn more about automated synthetic chemistry with applications in drug delivery and modern formulation of therapeutic peptides and oligonucleotides.
References:
[1] S. Cogoi, U. Jakobsen, E. B. Pedersen, S. Vogel & L. E. Xodo, Lipid-modified G4-decoy oligonucleotide anchored to nanoparticles: delivery and bioactivity in pancreatic cancer cells Sci. Rep. 2016, 6, 1-13.