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

International Journal of Molecular Sciences

Yi-Bing Huang²  Li-Yan He²  Hong-Yu Jiang¹ 

[1] The First Hospital, Jilin University, Changchun 130021, China;Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun 130012, China; E-Mails:

关键词: anticancer peptides;    helicity;    hydrophobicity;    mechanism of action;    specificity;   

DOI  :  10.3390/ijms13066849

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.