Design, synthesis and DNA interactions of a chimera between a platinum complex and an IHF mimicking peptide.

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Design, synthesis and DNA interactions of a chimera between a platinum complex and an IHF mimicking peptide. / Rao, Harita; Damian, Mariana; Alshiekh, Alak; Elmroth, Sofi; Diederichsen, Ulf.

I: Organic and Biomolecular Chemistry, Vol. 13, Nr. 48, 2015, s. 11704-11713.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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Rao, Harita ; Damian, Mariana ; Alshiekh, Alak ; Elmroth, Sofi ; Diederichsen, Ulf. / Design, synthesis and DNA interactions of a chimera between a platinum complex and an IHF mimicking peptide. I: Organic and Biomolecular Chemistry. 2015 ; Vol. 13, Nr. 48. s. 11704-11713.

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TY - JOUR

T1 - Design, synthesis and DNA interactions of a chimera between a platinum complex and an IHF mimicking peptide.

AU - Rao, Harita

AU - Damian, Mariana

AU - Alshiekh, Alak

AU - Elmroth, Sofi

AU - Diederichsen, Ulf

PY - 2015

Y1 - 2015

N2 - Conjugation of metal complexes with peptide scaffolds possessing high DNA binding affinity has shown to modulate their biological activities and to enhance their interaction with DNA. In this work, a platinum complex/peptide chimera was synthesized based on a model of the Integration Host Factor (IHF), an architectural protein possessing sequence specific DNA binding and bending abilities through its interaction with a minor groove. The model peptide consists of a cyclic unit resembling the minor grove binding subdomain of IHF, a positively charged lysine dendrimer for electrostatic interactions with the DNA phosphate backbone and a flexible glycine linker tethering the two units. A norvaline derived artificial amino acid was designed to contain a dimethylethylenediamine as a bidentate platinum chelating unit, and introduced into the IHF mimicking peptides. The interaction of the chimeric peptides with various DNA sequences was studied by utilizing the following experiments: thermal melting studies, agarose gel electrophoresis for plasmid DNA unwinding experiments, and native and denaturing gel electrophoresis to visualize non-covalent and covalent peptide-DNA adducts, respectively. By incorporation of the platinum metal center within the model peptide mimicking IHF we have attempted to improve its specificity and DNA targeting ability, particularly towards those sequences containing adjacent guanine residues.

AB - Conjugation of metal complexes with peptide scaffolds possessing high DNA binding affinity has shown to modulate their biological activities and to enhance their interaction with DNA. In this work, a platinum complex/peptide chimera was synthesized based on a model of the Integration Host Factor (IHF), an architectural protein possessing sequence specific DNA binding and bending abilities through its interaction with a minor groove. The model peptide consists of a cyclic unit resembling the minor grove binding subdomain of IHF, a positively charged lysine dendrimer for electrostatic interactions with the DNA phosphate backbone and a flexible glycine linker tethering the two units. A norvaline derived artificial amino acid was designed to contain a dimethylethylenediamine as a bidentate platinum chelating unit, and introduced into the IHF mimicking peptides. The interaction of the chimeric peptides with various DNA sequences was studied by utilizing the following experiments: thermal melting studies, agarose gel electrophoresis for plasmid DNA unwinding experiments, and native and denaturing gel electrophoresis to visualize non-covalent and covalent peptide-DNA adducts, respectively. By incorporation of the platinum metal center within the model peptide mimicking IHF we have attempted to improve its specificity and DNA targeting ability, particularly towards those sequences containing adjacent guanine residues.

U2 - 10.1039/c5ob01885d

DO - 10.1039/c5ob01885d

M3 - Article

C2 - 26477860

VL - 13

SP - 11704

EP - 11713

JO - Organic and Biomolecular Chemistry

JF - Organic and Biomolecular Chemistry

SN - 1477-0539

IS - 48

ER -