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DNA condensation with a boron-containing cationic peptide for modeling boron neutron capture therapy

The amino acid derivative 4-borono-L-phenylalanine (BPA) has been used in the radiation medicine technique boron neutron capture therapy (BNCT). Here we have characterized its interaction with DNA when incorporated into a positively charged hexa-L-arginine peptide. This ligand binds strongly to DNA...

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Bibliographic Details
Published in:Radiation physics and chemistry (Oxford, England : 1993) England : 1993), 2020-01, Vol.166, p.108521, Article 108521
Main Authors: Perry, Chris C., Ramos-Méndez, Jose, Milligan, Jamie R.
Format: Article
Language:English
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Summary:The amino acid derivative 4-borono-L-phenylalanine (BPA) has been used in the radiation medicine technique boron neutron capture therapy (BNCT). Here we have characterized its interaction with DNA when incorporated into a positively charged hexa-L-arginine peptide. This ligand binds strongly to DNA and induces its condensation, an effect which is attenuated at higher ionic strengths. The use of an additional tetra-L-arginine ligand enables the preparation of a DNA condensate in the presence of a negligible concentration of unbound boron. Under these conditions, Monte Carlo simulation indicates that >85% of energy deposition events resulting from thermal neutron irradiation derive from boron fission. The combination of experimental model systems and simulations that we describe here provides a valuable tool for accurate track structure modeling of the DNA damage produced by the high LET particles involved in BNCT. •Boron-containing cationic peptide that binds strongly to DNA.•Peptide condensed DNA models cellular chromatin.•Boron concentration in condensed DNA within the therapeutic range.•Vast majority of energy deposition is from neutron capture on boron.
ISSN:0969-806X
1879-0895
DOI:10.1016/j.radphyschem.2019.108521