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

1email, 1email, 2,* email and 1,* email
Received: 20 April 2012; in revised form: 19 May 2012 / Accepted: 22 May 2012 / Published: 5 June 2012
(This article belongs to the Special Issue Advances in Molecular Oncology)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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
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MDPI and ACS Style

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.

AMA Style

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. International Journal of Molecular Sciences. 2012; 13(6):6849-6862.

Chicago/Turabian Style

Huang, Yi-Bing; He, Li-Yan; Jiang, Hong-Yu; Chen, Yu-Xin. 2012. "Role of Helicity on the Anticancer Mechanism of Action of Cationic-Helical Peptides." Int. J. Mol. Sci. 13, no. 6: 6849-6862.

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