The doctoral dissertations of the former Helsinki University of Technology (TKK) and Aalto University Schools of Technology (CHEM, ELEC, ENG, SCI) published in electronic format are available in the electronic publications archive of Aalto University - Aaltodoc.
Aalto

Multivalent Dendrons for High-Affinity DNA Binding

Mauri Kostiainen

Dissertation for the degree of Doctor of Science in Technology to be presented with due permission of the Faculty of Information and Natural Sciences for public examination and debate in Auditorium AS1 at Helsinki University of Technology (Espoo, Finland) on the 29th of May, 2008, at 12 noon.

Overview in PDF format (ISBN 978-951-22-9372-8)   [2975 KB]
Dissertation is also available in print (ISBN 978-951-22-9371-1)

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.

This thesis consists of an overview and of the following 5 publications:

  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.
  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.
  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.
  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.
  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.

Keywords: self-assembly, dendrimers, dendron, DNA, protein

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© 2008 Helsinki University of Technology

Last update 2011-05-26