Small Molecule-Peptide Conjugates as Dimerization Inhibitors of Leishmania infantum Trypanothione Disulfide Reductase

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...

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Detalles Bibliográficos
Autores: Revuelto Pérez, Alejandro, López Martín, Isabel, Lucio Ortega, Héctor Elessar de|||0000-0002-9840-0779, García Soriano, Juan Carlos, Zanda, Nicola, Castro de la Osa, Sonia de, Gago Badenas, Federico|||0000-0002-3071-4878, Jiménez Ruiz, Antonio|||0000-0001-8238-3081, Velázquez Díaz, Sonsoles, Camarasa Rius, María José
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad de Alcalá (UAH)
Repositorio:e_Buah Biblioteca Digital Universidad de Alcalá
Idioma:inglés
OAI Identifier:oai:ebuah.uah.es:10017/59041
Acceso en línea:http://hdl.handle.net/10017/59041
https://dx.doi.org/10.3390/ph14070689
Access Level:acceso abierto
Palabra clave:leishmaniasis
small molecule¿peptide conjugates
dimerization inhibitors
trypanothione disulfide reductase
Medicina
Medicine
Descripción
Sumario: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 Leishmania infantum TryR (LiTryR) offered an innovative and so far unexploited opportunity for the development of novel antileishmanial agents. Now, we show that linking our previous peptide prototype TRL38 to selected hydrophobic moieties provides a novel series of small-molecule-peptide conjugates that behave as good inhibitors of both LiTryR activity and dimerization.

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