Synthesis and Characterization of the Conjugated Peptide Lunatin-Folate

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, a...

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Main Authors: Amanda Neves de Souza, Adriano Monteiro de Castro Pimenta, Rodrigo Moreira Verly
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:Organics
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Online Access:https://www.mdpi.com/2673-401X/6/1/8
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author Amanda Neves de Souza
Adriano Monteiro de Castro Pimenta
Rodrigo Moreira Verly
author_facet Amanda Neves de Souza
Adriano Monteiro de Castro Pimenta
Rodrigo Moreira Verly
author_sort Amanda Neves de Souza
collection DOAJ
description 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-<sub>NH2</sub>, 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-<sub>NH2</sub>, 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.
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spelling doaj-art-22ffcf1367b64e05b0f37941648fb13b2025-08-20T02:42:28ZengMDPI AGOrganics2673-401X2025-02-0161810.3390/org6010008Synthesis and Characterization of the Conjugated Peptide Lunatin-FolateAmanda Neves de Souza0Adriano Monteiro de Castro Pimenta1Rodrigo Moreira Verly2Departamento de Química, Faculdade de Ciências Exatas, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM)—Campus JK, Diamantina 39100-000, MG, BrazilDepartamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, BrazilDepartamento de Química, Faculdade de Ciências Exatas, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM)—Campus JK, Diamantina 39100-000, MG, BrazilBioactive 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-<sub>NH2</sub>, 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-<sub>NH2</sub>, 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.https://www.mdpi.com/2673-401X/6/1/8Lunatin-1antimicrobial peptideCu-catalyzed azide?alkyne cycloadditionpeptide–drug conjugate
spellingShingle Amanda Neves de Souza
Adriano Monteiro de Castro Pimenta
Rodrigo Moreira Verly
Synthesis and Characterization of the Conjugated Peptide Lunatin-Folate
Organics
Lunatin-1
antimicrobial peptide
Cu-catalyzed azide?alkyne cycloaddition
peptide–drug conjugate
title Synthesis and Characterization of the Conjugated Peptide Lunatin-Folate
title_full Synthesis and Characterization of the Conjugated Peptide Lunatin-Folate
title_fullStr Synthesis and Characterization of the Conjugated Peptide Lunatin-Folate
title_full_unstemmed Synthesis and Characterization of the Conjugated Peptide Lunatin-Folate
title_short Synthesis and Characterization of the Conjugated Peptide Lunatin-Folate
title_sort synthesis and characterization of the conjugated peptide lunatin folate
topic Lunatin-1
antimicrobial peptide
Cu-catalyzed azide?alkyne cycloaddition
peptide–drug conjugate
url https://www.mdpi.com/2673-401X/6/1/8
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AT adrianomonteirodecastropimenta synthesisandcharacterizationoftheconjugatedpeptidelunatinfolate
AT rodrigomoreiraverly synthesisandcharacterizationoftheconjugatedpeptidelunatinfolate