SECUAH 2023 > García-Marín etal 2023

dianas | Vol 12 No 1 | marzo 2023 | e202303cp01

New strategies in chronic kidney disease: a study of the ILK–parvin protein-protein interaction towards new drugs.

Javier García-Marín, Mercedes Griera, Sergio de Frutos, Ramon Alajarín, Manuel Rodríguez-Puyol, Diego Rodríguez-Puyol, Juan J. Vaquero

Universidad de Alcalá, Facultad de Farmacia, Carretera Madrid-Barcelona, Km 33, 100, 28805 Alcalá de Henares, Madrid, España

javier.garciamarin@uah.es

VIII Congreso de Señalización Celular, SECUAH 2022.
21 a 24 de marzo, 2023. Universidad de Alcalá. Alcalá de Henares, Madrid. España.

Keywords: Integrin-linked kinase; protein-protein interaction; peptide synthesis; ILK; chronic kidney disease

Abstract

Chronic kidney disease (CKD) is the non-transmissible global cause of death that has raised the most within the past 20 years. It increases the risk of all-cause mortality and may progress to end stage of renal failure. There is no effective therapy for CKD and current approaches do not prevent its progression. Then, the search of new and validated targets against CKD has become a milestone in academic groups and industry. This pathology has been related, at least partially, to integrin-linked kinase (ILK). This is an intracellular pseudokinase that forms the ternary complex IPP (ILK–PINCH–parvin) with two adaptor proteins. On the other hand, in the last few years, protein-protein interaction has emerged as a fruitful source for new potent and selective drugs. We have focused our efforts on the study of ILK-parvin interaction to generate a new family of peptides that, eventually, may validate this protein as a direct target for CKD. Starting from the crystal structure, an extensive in silico analysis on the interaction surface was carried to propose a decoy peptide based on α-parvin. These data have allowed the design and synthesis of new peptides which probed its mechanism of action within human mesangial cells by its direct union to ILK. In addition, fluorescently labeled peptides have shown the ability to enter the cell and support in cellulo-based experiments.