Peptide Dimerization as a Strategy for the Development of Antileishmanial Compounds

Author(s)

Coelho, Natalia C. S. ; Portuondo, Deivys L. F. ; Lima, Jhonatan ; Velasquez, Angela M. A. ; Valente, Valeria ; Carlos, Iracilda Z. ; Cilli, Eduardo M. ; Graminha, Marcia A. S.

• Document type: Journal article
• Source: Molecules; v. 29, n. 21, p. 21-pg., 2024-11-01.

Abstract

Leishmaniasis is recognized as a serious public health problem in Brazil and around the world. The limited availability of drugs for treatment, added to the diversity of side effects and the emergence of resistant strains, shows the importance of research focused on the development of new molecules, thus contributing to treatments. Therefore, this work aimed to identify leishmanicidal compounds using a peptide dimerization strategy, as well as to understand their mechanisms of action. Herein, it was demonstrated that the dimerization of the peptide TSHa, (TSHa)2K, presented higher potency and selectivity than its monomeric form when evaluated against Leishmania mexicana and Leishmania amazonensis. Furthermore, these compounds are capable of inhibiting the parasite cysteine protease, an important target explored for the development of antileishmanial compounds, as well as to selectively interact with the parasite membranes, as demonstrated by flow cytometry, permeabilization, and fluorescence microscopy experiments. Based on this, the identified molecules are candidates for use in in vivo studies with animal models to combat leishmaniasis. (AU)

• FAPESP's process: 20/04415-4 - Therapeutics for leishmaniasis: from screening to the study of mechanisms of action, a contribution to the discovery of new antileishmanial molecules
• Grantee: Marcia Aparecida Silva Graminha
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/05411-8 - Development of peptide/guanidine bioconjugates with anti-Leishmania activity
• Grantee: Eduardo Maffud Cilli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC