Peptide-based drug systems

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Tezin Türü: Doktora

Tezin Yürütüldüğü Kurum: Orta Doğu Teknik Üniversitesi, Fen Edebiyat Fakültesi, Kimya Bölümü, Türkiye

Tezin Onay Tarihi: 2017

Öğrenci: MELEK PARLAK

Danışman: SALİH ÖZÇUBUKÇU

Özet:

The increasing appeal of safe, cheap and effective treatments against various type of diseases has paved the way for the discovery and development of innovative peptide-based drug and drug delivery systems. The relative ease with which peptide based-materials can be synthesized and the wide range of synthetic techniques available have ensured that these materials can be tuned to adopt specific conformation or modified to contain specific functional groups. Our major focus in this thesis is developing peptides with different scaffolds. In one study, we synthesized small peptides that mimic the correctly folded state of the fusion protein of the Respiratory syncytial virus (RSV) that causes respiratory tract infections. As small peptides generally do not retain their native conformation, they were stabilized through construction of intramolecular bridges that hold the peptides in the right conformation. A various type and size of intramolecular bridges were established in different part of the peptide sequences. Constrained peptides that both showing binding against specific antibodies and having helical structures as in their native structures were covalently linked to carrier protein for further immunological studies. In another study, poor therapeutic properties of pro-apoptotic Smac peptide (AVPIAQK) were improved. Apoptotic peptide was fused to a well-known octaarginine cell-penetrating peptide for promoting its access to a cell's interior. Smac and octaarginine containing linear, monocyclic and bicyclic peptides were successfully synthesized. The biological properties of designed peptides in terms of cell-permeability, cytotoxicity and apoptotic efficiency were studied. As a final study, anthracene containing peptide nanofibers and peptide vesicles were designed, synthesized and changes in their self-assembled structure upon light exposure at 365 nm were investigated. It was proved that such systems have a potential as light-driven drug delivery.