PhD Scientific Days 2022

Pharmaceutical Sciences II. (Poster discussion will take place in the Aula during the Coffee Break)

Synthesis of modified β-peptide foldamers

Text of the abstract

Synthesis of modified β-peptide foldamers
Introduction: Foldamers are biomimetic polymers that can self-organize to form a regular secondary structure using secondary binding forces. The most important representatives of peptidomimetic foldamers are β-peptides. Unlike traditional α peptides, β peptide foldamers have the advantage of greater stability over proteolysis/metabolism and a more stable secondary structure. The α and β carbon atoms can be substitutable in a variety of ways, with which a high degree of structural diversity is caused, and this also has a decisive influence on conformation behavior.
Aims: In our work, we set ourselves the goal of producing foldamers in which these self-organizing structural units can be found between the dynamically variable ordered helix and between an unordered stretched conformation.
Method: To produce β peptide solid-phase peptide synthesis was used, in which we attached the first amino acid to a solid substrate (resin), then attached the next amino acid, and finally cleavage the finished sequence from the resin. After a retro-Diels-Alder reaction within the β peptide, we formed a double bond and obtained a compound with a stretched structure, not a helically arranged secondary structure. Performed a bromination in an aqueous solution, we received a bromine hidrine derivative, which allows for self-organization with a helical structure. If we treat the resulting molecule with metal zinc, we can get back the disordered structure containing a double bond. The cleaning of the molecule was carried out with a semi-preparatory HPLC of reverse phase (C18). This allowed us to separate pollutants and by-products from our sample.
Results: In the first step, we produced and cleaned the desired β peptide. In the second phase of our research, we successfully carried out the draft reactions, which were confirmed by analytical methods.
Conclusion: By periodically changing the above-mentioned reactions and conditions, we were able to create a dynamic structure, which can practically be considered a nano spring. For future applications, among others, it can play an important role in the creation of molecular machines and forces, which may even play a role in molecular surgery.


eeszter99@gmail.com
Semmelweis Egyetem, Semmelweis Egyetem Doktori Iskola, Gyógyszertudományok
Dr. Mándity István ,Ph.D.