PhD Scientific Days 2022

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

Conformational study of cell-penetrating peptides

Text of the abstract

Conformational study of cell-penetrating peptides

Introduction
Cell-penetrating peptides (CPP) are capable translocating trough biological membranes without damaging them so they are suitable to carry various compounds into cells (even into the nucleus) and for transcellular transport. Our in silico molecular modelling studies are focusing on three CPP with open backbone, including the penetratin, a naturally occurring oligopeptide and two of its modified sequence analogues and three further natural CPPs with cyclic backbone.

Aims
The goal of the research is to examine the conjugates of these peptides with different active ingredients (doxorubicine, azidothymidine phosphate, rasagiline) as transport systems which are meant to reach intracellular targets.

Method
We carried out molecular dynamics simulations in order to examine the behavior of the conjugated and unconjugated peptides in a system with explicit water and membrane models utilizing the Desmond module of the Schrödinger program package.

Results
Our simulations showed that the interaction of the penetratin with the membrane led to spectacular rearrangements in the peptide structure while the cyclic peptides remained unchanged due their strong conformational stability. According to our studies so far the covalently conjugated drug compounds did not influence the penetration properties of the peptides significantly.

Conclusion
Although our simulations did not model the mechanism of the membrane penetration the way as we expected yet our results may contribute to better understanding the mechanism of cell-penetrating peptides which could serve as basis for delivering conjugated drug molecules to their intracellular targets.

Funding
The project is financed by research framework and the budget of the Department of Organic Chemistry.

E-mail: ivanczi.marton@pharma.semmelweis-univ.hu
Semmelweis University Doctoral School of Pharmaceutical Sciences
Supervisor: Dr. István Mándity associate professor
Consulent: Dr. Balázs Balogh assistant professor