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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 LU ; Alshiekh, Alak LU ; Elmroth, Sofi LU and Diederichsen, Ulf (2015) In Organic and Biomolecular Chemistry 13(48). p.11704-11713
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Organic and Biomolecular Chemistry
volume
13
issue
48
pages
11704 - 11713
publisher
Royal Society of Chemistry
external identifiers
  • pmid:26477860
  • wos:000366021300014
  • scopus:84948661330
ISSN
1477-0539
DOI
10.1039/c5ob01885d
language
English
LU publication?
yes
id
05ca07b7-cedd-4668-ae5f-88d1bfcab2f6 (old id 8149033)
date added to LUP
2015-11-16 14:29:22
date last changed
2017-01-01 03:03:22
@article{05ca07b7-cedd-4668-ae5f-88d1bfcab2f6,
  abstract     = {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.},
  author       = {Rao, Harita and Damian, Mariana and Alshiekh, Alak and Elmroth, Sofi and Diederichsen, Ulf},
  issn         = {1477-0539},
  language     = {eng},
  number       = {48},
  pages        = {11704--11713},
  publisher    = {Royal Society of Chemistry},
  series       = {Organic and Biomolecular Chemistry},
  title        = {Design, synthesis and DNA interactions of a chimera between a platinum complex and an IHF mimicking peptide.},
  url          = {http://dx.doi.org/10.1039/c5ob01885d},
  volume       = {13},
  year         = {2015},
}