Identification and characterization of a bactericidal and proapoptotic peptide from cycas revoluta seeds with DNA binding properties

Santi M. Mandal, Ludovico Migliolo, Subhasis Das, Mahitosh Mandal, Octavio L. Franco, Tapas Hazra

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Nowadays, novel pharmacies have been screened from plants. Among them are the peptides, which show multiple biotechnological activities. In this report, a small peptide (Ala-Trp-Lys-Leu-Phe-Asp-Asp-Gly-Val) with a molecular mass of 1,050 Da was purified from Cycas revoluta seeds by using reversed-phase liquid chromatography. This peptide shows clear deleterious effects against human epidermoid cancer (Hep2) and colon carcinoma cells (HCT15). It caused inhibition of cancer cell proliferation and further disruption of nucleosome structures, inducing apoptosis by direct DNA binding. A remarkable antibacterial activity was also observed in this same peptide. Nevertheless, no significant lysis of normal RBC cells was observed in the presence of peptide. Additionally, an acetylation at the N-termini portion is able to reduce both activities. Bioinformatics tools were also utilized for construction of a three-dimensional model showing a single amphipathic helix. Since in vitro binding studies show that the target of this peptide seems to be DNA, theoretical docking studies were also performed to better understand the interaction between peptide and nucleic acids and also to shed some light on the acetyl group role. Firstly, binding studies showed that affinity contacts basically occur due to electrostatic attraction. The complex peptide-ssDNA was clearly oriented by residues Ala 1, Lys 3, and Asp 6, which form several hydrogen bonds that are able to stabilize the complex. When acetyl was added, hydrogen bonds are broken, reducing the peptide affinity. In summary, it seems that information here provided could be used to design a novel derivative of this peptide which a clear therapeutic potential.

Original languageEnglish (US)
Pages (from-to)184-193
Number of pages10
JournalJournal of Cellular Biochemistry
Volume113
Issue number1
DOIs
StatePublished - Jan 2012

Fingerprint

Cycas
Seed
Seeds
Peptides
DNA
Hydrogen
Hydrogen bonds
Peptide Nucleic Acids
Acetylation
Nucleosomes
Pharmacies
Liquid chromatography
Cell proliferation
Molecular mass
Reverse-Phase Chromatography
Bioinformatics
Computational Biology
Static Electricity
Colonic Neoplasms
Electrostatics

Keywords

  • Anticancer peptide
  • Antimicrobial peptides
  • DNA affinity
  • Molecular modeling
  • Plant peptides

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Identification and characterization of a bactericidal and proapoptotic peptide from cycas revoluta seeds with DNA binding properties. / Mandal, Santi M.; Migliolo, Ludovico; Das, Subhasis; Mandal, Mahitosh; Franco, Octavio L.; Hazra, Tapas.

In: Journal of Cellular Biochemistry, Vol. 113, No. 1, 01.2012, p. 184-193.

Research output: Contribution to journalArticle

Mandal, Santi M. ; Migliolo, Ludovico ; Das, Subhasis ; Mandal, Mahitosh ; Franco, Octavio L. ; Hazra, Tapas. / Identification and characterization of a bactericidal and proapoptotic peptide from cycas revoluta seeds with DNA binding properties. In: Journal of Cellular Biochemistry. 2012 ; Vol. 113, No. 1. pp. 184-193.
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