Small Molecule-Peptide Conjugates as Dimerization Inhibitors of <i>Leishmania infantum</i> Trypanothione Disulfide Reductase

• Main Authors: Alejandro Revuelto (Author), Isabel López-Martín (Author), Héctor de Lucio (Author), Juan Carlos García-Soriano (Author), Nicola Zanda (Author), Sonia de Castro (Author), Federico Gago (Author), Antonio Jiménez-Ruiz (Author), Sonsoles Velázquez (Author), María-José Camarasa (Author)
• Format: Book
• Published: MDPI AG, 2021-07-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Trypanothione disulfide reductase (TryR) is an essential homodimeric enzyme of trypanosomatid parasites that has been validated as a drug target to fight human infections. Using peptides and peptidomimetics, we previously obtained proof of concept that disrupting protein-protein interactions at the dimer interface of <i>Leishmania infantum</i> TryR <i>(Li</i>TryR<i>)</i> offered an innovative and so far unexploited opportunity for the development of novel antileishmanial agents. Now, we show that linking our previous peptide prototype <b>TRL38</b> to selected hydrophobic moieties provides a novel series of small-molecule-peptide conjugates that behave as good inhibitors of both <i>Li</i>TryR activity and dimerization.

Item Description

10.3390/ph14070689
1424-8247