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A conjugate of the lytic peptide Hecate and gallic acid: structure, activity against cervical cancer, and toxicity

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Abstract

Conjugate compounds constitute a new class of molecules of important biological interest mainly for the treatment of diseases such as cancer. The N-terminus region of cationic peptides has been described as important for their biological activity. The aim of this study was to evaluate the lytic peptide Hecate (FALALKALKKALKKLKKALKKAL) and the effect of conjugating this macromolecule with gallic acid (C7H6O5) in terms of structure, anti-cancer activity, and toxicity. An N-terminus GA-Hecate peptide conjugate was synthesized to provide information regarding the relationship between the amino-terminal region and its charge and the secondary structure and biological activity of the peptide; and the effects of gallic acid on these parameters. Peptide secondary structure was confirmed using circular dichroism (CD). The CD measurements showed that the peptide has a high incidence of α-helical structures in the presence of SDS and LPC, while GA-Hecate presented lower incidence of α-helical structures in the same chemical environment. An evaluation of the anti-cancer activity in HeLa cancer cells indicated that both peptides are active, but that coupling gallic acid at the N-terminus decreased the activity of the free peptide. GA-Hecate showed lower activity in non-tumor keratinocyte cells but higher hemolytic activity. Our findings suggest that the N-terminus of Hecate plays an important role in its activity against cervical cancer by affecting it secondary structure, toxicity, and hemolytic activity. This study highlights the importance of the N-terminus in antitumor activity and could provide an important tool for developing new anti-cancer drugs.

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Acknowledgments

The authors are grateful to the Conselho Nacional de Desenvolvimento Científico (CNPq) and Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP) for financial support.

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The authors declare that they have no conflict of intrest.

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Authors and Affiliations

  1. Department of Biochemistry and Chemical Technology, Institute of Chemistry, UNESP, Univ Estadual Paulista, Araraquara, SP, CEP 14800-060, Brazil

    Paulo R. S. Sanches, Esteban N. Lorenzón & Eduardo Maffud Cilli

  2. Instituto de Biociências, Letras e Ciências Exatas, UNESP, Univ Estadual Paulista, S.J.Rio Preto, SP, Brazil

    Bruno M. Carneiro, Mariana N. Batista, Ana Cláudia S. Braga & Paula Rahal

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  1. Paulo R. S. Sanches
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  2. Bruno M. Carneiro
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  3. Mariana N. Batista
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  4. Ana Cláudia S. Braga
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  5. Esteban N. Lorenzón
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  6. Paula Rahal
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  7. Eduardo Maffud Cilli
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Correspondence to Eduardo Maffud Cilli.

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Sanches, P.R.S., Carneiro, B.M., Batista, M.N. et al. A conjugate of the lytic peptide Hecate and gallic acid: structure, activity against cervical cancer, and toxicity. Amino Acids 47, 1433–1443 (2015). https://doi.org/10.1007/s00726-015-1980-7

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