Design, synthesis and DNA interactions of a chimera between a platinum complex and an IHF mimicking peptide.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8149033
- author
- Rao, Harita ; Damian, Mariana LU ; Alshiekh, Alak LU ; Elmroth, Sofi LU and Diederichsen, Ulf
- organization
- publishing date
- 2015
- 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
- pmid:26477860
- 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
- 2016-04-01 09:51:20
- date last changed
- 2022-04-27 08:13:05
@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}},
doi = {{10.1039/c5ob01885d}},
volume = {{13}},
year = {{2015}},
}