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Research Article Open access CC BY 4.0

Synthesis and Characterization of the Conjugated Peptide Lunatin-Folate

Amanda Neves de Souza, Adriano Monteiro de Castro Pimenta, Rodrigo Moreira Verly

Organics · pp. 8–8 · Published 11 Feb 2025

10.3390/org6010008

Abstract

Bioactive peptides are promising therapeutic agents due to their antimicrobial and anticancer activities, although their lack of selectivity often limits clinical applications. This study demonstrates the optimal synthetic route for conjugating folic acid (FA) with the bioactive peptide Lunatin-1, aiming to improve selectivity for neoplastic cells. The synthesis combines solid-phase peptide synthesis (SPPS) and Cu(I)-catalyzed cycloaddition to link folic acid to Lunatin-1 via a triazole ring. Using the model tripeptide FIG-NH2, key intermediates and the final product were characterized by high-performance liquid chromatography (HPLC), mass spectrometry (MALDI-ToF), Fourier-transform infrared spectroscopy (FTIR), and nuclear magnetic resonance (NMR). Reaction yields and purity were optimized with FIG-NH2, providing a reproducible synthesis pathway. Additionally, the results confirmed successful conjugation, with the FA-Trz-Luna product exhibiting molecular integrity and structural stability, as validated by spectral analyses. This study highlights a potential synthesis route for peptide-folate conjugates to be used as selective and multifunctional therapeutic agents, laying the groundwork for biological evaluations of their cytotoxicity and antimicrobial properties.

Conjugated system Peptide Characterization (materials science) Chemistry Folic acid Combinatorial chemistry Computational biology Biochemistry

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