Optically degradable dendrons for temporary adhesion of proteins to DNA

Mauri A. Kostiainen (Corresponding Author), Juha Kotimaa, Marja-Leena Laukkanen, Giovanni P. Pavan

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26 Citations (Scopus)

Abstract

Experimental studies and molecular dynamics modeling demonstrate that multivalent dendrons can be used to temporarily glue proteins and DNA together with high affinity. We describe N‐maleimide‐cored polyamine dendrons that can be conjugated with free cysteine residues on protein surfaces through 1,4‐conjugate addition to give one‐to‐one protein–polymer conjugates. We used a genetically engineered cysteine mutant of class II hydrophobin (HFBI) and a single‐chain Fragment variable (scFv) antibody as model proteins for the conjugation reactions. The binding affinity of the protein–dendron conjugates towards DNA was experimentally assessed by using the ethidium bromide displacement assay. The binding was found to depend on the generation of the dendron, with the second generation having a stronger affinity than the first generation. Thermodynamic parameters of the binding were obtained from molecular dynamics modeling, which showed that the high binding affinity for each system is almost completely driven by a strong favorable binding enthalpy that is opposed by unfavorable binding entropy. A short exposure to UV (λ≈350 nm) can cleave the photolabile o‐nitrobenzyl‐linked binding ligands from the surface of the dendron, which results in loss of the multivalent binding interactions and triggers the release of the DNA and protein. The timescale of the release is very rapid and the binding partners can be efficiently released after 3 min of UV exposure.
Original languageEnglish
Pages (from-to)6912-6918
Number of pages7
JournalChemistry - A European Journal
Volume16
Issue number23
DOIs
Publication statusPublished - 2010
MoE publication typeA1 Journal article-refereed

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Keywords

  • dendrimers
  • DNA
  • multivalency
  • protein modifications
  • self-assembly

Cite this

Kostiainen, M. A., Kotimaa, J., Laukkanen, M-L., & Pavan, G. P. (2010). Optically degradable dendrons for temporary adhesion of proteins to DNA. Chemistry - A European Journal, 16(23), 6912-6918. https://doi.org/10.1002/chem.201000091