A theoretical analysis of secondary structural characteristics of anticancer peptides (original) (raw)

Abstract

Here, cluster analysis showed that a database of 158 anticancer peptides formed 21 clusters based on net positive charge, hydrophobicity and amphiphilicity. In general, these clusters showed similar median toxicities (P = 0.176) against eukaryotic cell lines and no single combination of these properties was found optimal for efficacy. The database contained 14 peptides, which showed selectivity for tumour cell lines only (ACPCT), 123 peptides with general toxicity to eukaryotic cells (ACPGT) and 21 inactive peptides (ACPI). Hydrophobic arc size analysis showed that there was no significant difference across the datasets although peptides with wide hydrophobic arcs (>270°) appeared to be associated with decreased toxicity. Extended hydrophobic moment plot analysis predicted that over 50% of ACPCT and ACPGT peptides would be surface active, which led to the suggestion that amphiphilicity is a key driver of the membrane interactions for these peptides but probably plays a role in their efficacy rather than their selectivity. This analysis also predicted that only 14% of ACPCT peptides compared to 45% of ACPGT peptides were candidates for tilted peptide formation, which led to the suggestion that the absence of this structure may support cancer cell selectivity. However, these analyses predicted that ACPI peptides, which possess no anticancer activity, would also form surface active and tilted α-helices, clearly showing that other factors are involved in determining the efficacy and selectivity of ACPs.

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Abbreviations

ACP:

Anticancer peptides

ACPGT :

Anticancer peptides with general toxicity

ACPCT :

Anticancer peptides with selectivity to tumour cell lines

ACPI :

Inactive peptides

〈μH〉:

Mean hydrophobic moment

〈H〉:

Mean hydrophobicity

H0 :

Null hypothesis

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Acknowledgement

The authors would like to thank Dr Nadia Chuzhanova, University of Central Lancashire for her assistance with the cluster analysis.

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Authors and Affiliations

  1. School of Pharmacy and Pharmaceutical Science, University of Central Lancashire, Preston, PR1-2HE, UK
    Sarah R. Dennison & Jaipaul Singh
  2. School of Forensic and Investigative Sciences, University of Central Lancashire, Preston, PR1-2HE, UK
    Frederick Harris, Tailap Bhatt & Jaipaul Singh
  3. University of Central Lancashire, Preston, PR1-2HE, UK
    David A. Phoenix

Authors

  1. Sarah R. Dennison
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  2. Frederick Harris
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  3. Tailap Bhatt
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  4. Jaipaul Singh
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  5. David A. Phoenix
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Corresponding author

Correspondence toDavid A. Phoenix.

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Dennison, S.R., Harris, F., Bhatt, T. et al. A theoretical analysis of secondary structural characteristics of anticancer peptides.Mol Cell Biochem 333, 129–135 (2010). https://doi.org/10.1007/s11010-009-0213-3

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