5 research outputs found
Design of Bivalent Nucleic Acid Ligands for Recognition of RNA-Repeated Expansion Associated with Huntington’s Disease
We
report the development of a new class of nucleic acid ligands
that is comprised of Janus bases and the MPγPNA backbone and
is capable of binding rCAG repeats in a sequence-specific and selective
manner via, inference, bivalent H-bonding interactions. Individually,
the interactions between ligands and RNA are weak and transient. However,
upon the installation of a C-terminal thioester and an N-terminal
cystine and the reduction of disulfide bond, they undergo template-directed
native chemical ligation to form concatenated oligomeric products
that bind tightly to the RNA template. In the absence of an RNA target,
they self-deactivate by undergoing an intramolecular reaction to form
cyclic products, rendering them inactive for further binding. The
work has implications for the design of ultrashort nucleic acid ligands
for targeting rCAG-repeat expansion associated with Huntington’s
disease and a number of other related neuromuscular and neurodegenerative
disorders