Construction of a Reduction‐responsive DNA Microsphere using a Reduction‐cleavable Spacer based on a Nitrobenzene Scaffold

Here, we describe the design and synthesis of a new reduction‐cleavable spacer (RCS) based on a nitrobenzene scaffold for constructing reduction‐responsive oligonucleotides according to standard phosphoramidite chemistry. In addition, we demonstrate that the introduction of the RCS in the middle of an oligonucleotide (30 nt) enables the construction of a self‐assembled microsphere capable of exhibiting a reduction‐responsive disassembly. A reduction‐cleavable spacer (RCS) is described containing a nitrobenzene scaffold that can be incorporated into a single‐stranded DNA sequence to enable the construction of a reduction‐responsive DNA architecture with spherical morphology at micrometer scale. The RCS could allow for the introduction of the reduction‐responsiveness into various functional oligonucleotides as well as nucleic acid‐based architectures.