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Int. J. Mol. Sci. 2012, 13(6), 6849-6862; doi:10.3390/ijms13066849
Article

Role of Helicity on the Anticancer Mechanism of Action of Cationic-Helical Peptides

1
,
1
,
2,*  and 1,*
1 Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun 130012, China 2 The First Hospital, Jilin University, Changchun 130021, China
* Authors to whom correspondence should be addressed.
Received: 20 April 2012 / Revised: 19 May 2012 / Accepted: 22 May 2012 / Published: 5 June 2012
(This article belongs to the Special Issue Advances in Molecular Oncology (special issue))
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Abstract

In the present study, the 26-residue amphipathic α-helical peptide A12L/A20L (Ac-KWKSFLKTFKSLKKTVLHTLLKAISS-amide) with strong anticancer activity and specificity was used as the framework to study the effects of helicity of α-helical anticancer peptides on biological activities. Helicity was systematically modulated by introducing D-amino acids to replace the original L-amino acids on the non-polar face or the polar face of the helix. Peptide helicity was measured by circular dichroism spectroscopy and was demonstrated to correlate with peptide hydrophobicity and the number of D-amino acid substitutions. Biological studies showed that strong hemolytic activity of peptides generally correlated with high hydrophobicity and helicity. Lower helicity caused the decrease of anti-HeLa activity of peptides. By introducing D-amino acids to replace the original L-amino acids on the non-polar face or the polar face of the helix, we improved the therapeutic index of A12L/A20L against HeLa cells by 9-fold and 22-fold, respectively. These results show that the helicity of anticancer peptides plays a crucial role for biological activities. This specific rational approach of peptide design could be a powerful method to improve the specificity of anticancer peptides as promising therapeutics in clinical practices.
Keywords: anticancer peptides; helicity; hydrophobicity; mechanism of action; specificity anticancer peptides; helicity; hydrophobicity; mechanism of action; specificity
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Huang, Y.-B.; He, L.-Y.; Jiang, H.-Y.; Chen, Y.-X. Role of Helicity on the Anticancer Mechanism of Action of Cationic-Helical Peptides. Int. J. Mol. Sci. 2012, 13, 6849-6862.

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