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Labaditin, a cyclic peptide with rich biotechnological potential: preliminary toxicological studies and structural changes in water and lipid membrane environment

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Abstract

Cyclic peptides isolated from the plants of the Euphorbiaceae family have been largely studied due to their rigid conformation, which is considered significant for biologic activity. The peptide Labaditin (L0) and its open chain analogs (L1) were synthesized by the solid-phase peptide synthesis technique (Fmoc/tBu), and purified to elucidate its interaction with membrane models. A shift in λmax emission and Stern–Volmer constants values indicate that both tryptophans migrate to a more apolar environment, with L1 decreasing less than L0. A circular dichroism (CD) study revealed that L0 was kept unstructured in aqueous media as much as in the presence of dipalmitoilphosphatidylcholine liposomes. The thermodynamic studies by differential calorimetry (DSC) show a ΔH increase (50 and 18 kcal/mol, for L0 and L1, respectively) with peptide concentrations, which is indicative of lipids associating with peptides, resulting in the inability of the lipids to participate in the main transition. Therefore, all CD, DSC, and fluorescence data suggest a greater L0 membrane insertion. A probable mechanism for Labaditin interaction is based initially on the hydrophobic interaction of the peptide with the lipid membrane, conformational change, peptide adsorption on the lipid surface, and internalization process. Peptide’s antibacterial effect was also evaluated and revealed that only L0 showed reduction in viability in Gram-positive bacteria while no effects to the Gram-negative.

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Acknowledgments

The authors are grateful to Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação ao Amparo a Pesquisa do Estado de São Paulo (FAPESP), Coordenação de Aperfeiçoamento de Nível Superior—Projeto NanoBiotec (CAPES) for financial support and Priscila Cerviglieri for linguistic advice. PC, EMC and RGS are senior researchers of the CNPq, and SCB was the recipient of Master fellowship from FAPESP.

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  1. Departamento de Química, FFCLRP-USP, Ribeirão Preto, SP, Brazil

    S. C. Barbosa, Luis G. Dias & P. Ciancaglini

  2. Departamento de Bioquímica e Biotecnologia, IQ-UNESP-Univ. Estadual Paulista, Araraquara, SP, Brazil

    E. M. Cilli

  3. Centro de Estudos de Biomoléculas Aplicadas a Medicina (CEBio), Núcleo de Saúde (NUSAU), Universidade Federal de Rondônia (UNIR), Fundação Oswaldo Cruz Noroeste (FIOCRUZ), 76812-245, Porto Velho, RO, Brazil

    Rodrigo G. Stabeli

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Correspondence to P. Ciancaglini.

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Barbosa, S.C., Cilli, E.M., Dias, L.G. et al. Labaditin, a cyclic peptide with rich biotechnological potential: preliminary toxicological studies and structural changes in water and lipid membrane environment. Amino Acids 40, 135–144 (2011). https://doi.org/10.1007/s00726-010-0648-6

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