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- W2079304118 abstract "Antimicrobial peptides have gained interest as potential anti-cancer agents, e.g. inhibition of tumour growth in human prostate xenografts was shown by host defense like lytic peptides (1). We showed by Annexin V binding that, in prostate tumour cells, negatively charged phosphatidylserine (PS) accumulates in the outer plasma membrane leaflet, which normally resides in the inner leaflet. Thus, surface exposure of PS may make these cells susceptible to killing by these cationic peptides. The aim of this study is to develop short peptide sequences derived from NK-2, which was shown to have anti-tumour activity (2). NKCS (Cys of NK-2 exchanged by Ser) is composed of two α-helices connected with a hinge region. Initially we studied the interaction of the parent peptide and its N- and C-terminal part with membrane mimetic systems. Vesicle leakage experiments revealed that the N-terminal fragment exhibits similar affinity towards PS as NKCS. Thermodynamic experiments indicate that the N-terminal helix resembles the properties of NKCS. Furthermore, calorimetric studies revealed that NKCS and its fragments have no significant effect on the thermotropic behaviour of PC liposomes mimicking healthy mammalian cell membranes. Both circular dichroism and Monte-Carlo simulation using the bilayer parameters derived from our structural characterization of the lipid model systems showed that the selectivity for PS correlated with the alpha-helical content of the peptides. The C-terminal part was less structured showing lower affinity to PS containing membranes. Thus, the shorter N-terminal peptide can be used as a template for further optimization, as in vitro tests on a human prostate carcinoma cell line showed significant cell damage. (1) Papo N. et al., Cancer Res. 66 (2006) 5371-8. (2) Schröder-Borm H. et al., FEBS Lett. 579 (2005) 6128-61. Acknowledgement: EC - Marie-Curie Action: BIOCONTROL (MCRTN - 33439)" @default.
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- W2079304118 date "2010-01-01" @default.
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- W2079304118 title "Structural Aspects of the Interaction of Nk-2 Derived Peptides with Cancer Cells" @default.
- W2079304118 doi "https://doi.org/10.1016/j.bpj.2009.12.1514" @default.
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