Development of therapeutic peptide-loaded polymeric nano drug formulations and investigation of their structures with molecular modeling studies

Peptides are molecules that show great promise for the treatment of various diseases. They are important pharmaceutical compounds that can be used effectively with their therapeutic properties from cancer types to infectious diseases. These structures, which have important advantages such as being modifiable and strong binding affinity, have been especially preferred in nano-drug design studies. Tyr-Lys-Thr amino acids in the structure of YKT tripeptide used in this thesis have antibacterial, antiviral, anticancer, antioxidant properties. In the theoretical computation part of this thesis, it is aimed to carry out molecular modelling studies of Tyr-Lys-Thr tripeptide first and to develop nano-drug formulations using different polymers in the next stage. In molecular modelling studies, using the theoretical conformation analysis of the tripeptide, the most stable molecular geometry was determined, optimized and all fundamental vibration modes were determined, NBO, MEP, hyperpolarizability and HOMO-LUMO analyses were also performed. In the experimental part of the thesis, the optimal synthesis environments of YKT loaded chitosan and polycaprolactone (PCL) polymeric nanoparticles were created for MD calculations, and the interaction of the tripeptide with both chitosan and polycaprolactone (PCL) polymers and its dynamic behaviour in these environments were modelled. In addition, various pharmacokinetic properties of YKT, in which its potential to be used as a drug was determined by ADME analysis and its interactions with estrogen receptor, progesterone receptor, epidermal growth factor receptor, androgen receptor and DNA were determined by molecular docking programs. In the experimental part of the thesis, YKT loaded nanoparticles were synthesized with two different polymers, and characterization studies were carried out with imaging methods such as scanning electron microscopy and spectroscopic methods. Zeta potential, average particle size, polydispersity index analyses were performed, in vitro release profile was determined, encapsulation efficiency and loading capacity calculations were performed. In addition to these, the ability of YKT to bind to and cleave DNA was also demonstrated by experimental studies. Finally, the interactions of YKT tripeptide and YKT loaded nanoparticle formulations with two different surface charges with HeLa, MCF-7 and MAT-LyLu (MLL) cells in vitro cell culture medium and their cytotoxicity on these cells were evaluated.