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The ionization of a molecule into a molecular ion inside the mass spectrometer causes instability in the molecule's structure due to the loss of an electron. This eventually leads to the fragmentation or breaking of some bonds in the molecule. The fragmentation occurs predominantly at specific bonds to yield relatively stable fragments.
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The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
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Heterogeneous Rupturing Dendrimers.

Oliver C J Andrén1, Aristi P Fernandes2, Michael Malkoch1

  • 1School of Chemical Science and Engineering, Fiber and Polymer Technology, KTH Royal Institute of Technology , Teknikringen 56-58, SE-100 44 Stockholm, Sweden.

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|November 11, 2017
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Summary
This summary is machine-generated.

Dendrimers with disulfide bonds were designed to break apart into thiols inside cancer cells. This fragmentation increased reactive oxygen species (ROS), offering a new strategy for cancer treatment.

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Area of Science:

  • Supramolecular Chemistry
  • Nanotechnology
  • Medicinal Chemistry

Background:

  • Macromolecular scaffolds can template the synthesis of novel small molecules.
  • Dendrimers offer unique structural properties for controlled molecular release.

Purpose of the Study:

  • To synthesize dendrimers with internal disulfide bonds as macromolecular templates.
  • To demonstrate the selective disassembly of these dendrimers into constituent thiols.
  • To evaluate the potential of dendrimer fragmentation for intracellular reactive oxygen species (ROS) generation in cancer cells.

Main Methods:

  • Synthesis of disulfide-bridged dendrimers.
  • Stimuli-responsive disassembly using dithiothreitol (DTT).
  • Intracellular assessment of ROS levels in human lung carcinoma A549 cells.

Main Results:

  • Dendrimers successfully disassembled into defined thiol components (C3, CD2, DB2) under reducing conditions.
  • Dendrimer fragmentation led to a significant increase in intracellular ROS levels in A549 cells.
  • The orthogonal nature of DB2 functionality was confirmed.

Conclusions:

  • Disulfide-bridged dendrimers can act as flawless macromolecular templates.
  • Intracellular dendrimer disassembly can disrupt the cellular redox balance by increasing ROS.
  • These findings position dendrimers as potential prodrugs for ROS-mediated cancer therapy.