Multivalent dendrons for high-affinity DNA binding

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Doctoral thesis (article-based)
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Date
2008
Major/Subject
Mcode
Degree programme
Language
en
Pages
Verkkokirja (2975 KB, 52,[5] s.)
Series
TKK dissertations, 122
Abstract
In this Thesis the synthesis of various Newkome-type polyamine dendrons and their DNA binding properties is presented. These cationic dendrons bind DNA with extremely high affinity through multivalent ionic interactions. Dendrons with o-nitrobenzyl linked surface groups can be cleaved from the dendron framework by optical irradiation resulting in rapid release of the covalently bound surface groups and non-covalently bound DNA, due to dendron degradation and charge switching multivalency. N-maleimido cored dendrons can be attached onto protein surfaces in site-specific manner to yield exactly defined one-to-one protein-polymer conjugates, where the number of dendrons and their attachment site on the protein surface is precisely known. The resulting protein-dendron conjugates bind DNA with high affinity. Further studies in gene transfection, cytotoxicity and self-assembly establish relevance in gene therapy and surface patterning.
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Keywords
self-assembly, dendrimers, dendron, DNA, protein
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Parts
  • [Publication 1]: Mauri A. Kostiainen, John G. Hardy, and David K. Smith. 2005. High-affinity multivalent DNA binding by using low-molecular-weight dendrons. Angewandte Chemie International Edition, volume 44, number 17, pages 2556-2559.
  • [Publication 2]: John G. Hardy, Mauri A. Kostiainen, David K. Smith, Nathan P. Gabrielson, and Daniel W. Pack. 2006. Dendrons with spermine surface groups as potential building blocks for nonviral vectors in gene therapy. Bioconjugate Chemistry, volume 17, number 1, pages 172-178.
  • [Publication 3]: Mauri A. Kostiainen, David K. Smith, and Olli Ikkala. 2007. Optically triggered release of DNA from multivalent dendrons by degrading and charge-switching multivalency. Angewandte Chemie International Edition, volume 46, number 40, pages 7600-7604.
  • [Publication 4]: Mauri A. Kostiainen, Géza R. Szilvay, David K. Smith, Markus B. Linder, and Olli Ikkala. 2006. Multivalent dendrons for high-affinity adhesion of proteins to DNA. Angewandte Chemie International Edition, volume 45, number 21, pages 3538-3542.
  • [Publication 5]: Mauri A. Kostiainen, Géza R. Szilvay, Julia Lehtinen, David K. Smith, Markus B. Linder, Arto Urtti, and Olli Ikkala. 2007. Precisely defined protein-polymer conjugates: Construction of synthetic DNA binding domains on proteins by using multivalent dendrons. ACS Nano, volume 1, number 2, pages 103-113.
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