Design de novos péptidos dirigidos ao recetor de androgénio no cancro da mama triplo negativo: uma abordagem in silico

Ana Catarina Ramos Pires Pedrosa

Key information

Authors:

Ana Catarina Ramos Pires Pedrosa (Ana Catarina Ramos Pires Pedrosa)

Supervisors:

Maria Cristina Das Neves Oliveira (Maria Cristina das Neves Oliveira); João Domingos Galamba Correia (João Domingos Galamba Correia)

Published in

06/29/2022

Abstract

Breast cancer (BC) is still the leading cause of cancer death in women worldwide. A specific subtype of BC, known as triple negative breast cancer (TNBC) is frequently associated with a worse prognosis. Androgen receptor (AR) has been detected in 25%–35% of TNBC carcinoma cells. In these cases, the existence of peptides targeting this receptor represents a huge potential for diagnostic and/or therapeutic purposes. In this context, novel cellular penetrating peptides (CPPs) targeting AR were developed. The novel CPPs were developed through the CellPPD web-server and their uptake efficiency was predicted using MLCPP. The 3D structures of the peptides were predicted using the PEP-FOLD and I-TASSER web servers. Docking studies of the predicted AR-peptides complexes were performed in the HADDOCK web server to determine the peptides with the highest affinity to AR. The three most promising AR-binding peptides from docking studies were selected for molecular dynamics (MD) simulations. Based on the polar interactions, the percentage of the interface residues that interact, the HADDOCK-score, the root mean square deviation (RMSD), the CPP-score, and the uptake efficiency, the three most promising peptides selected were: Pep-19, Pep-23, and Pep-58. The MD simulations revealed that, of these three peptides, the one that shows the most potential is pep23 considering the conjugation of the different analyses: the RMSD, the root mean square fluctuation (RMSF), the hydrogen bonds, the binding free energy, and the solvent accessible area (SASA).