Conformational Selection in Anion Recognition: cGMP-Selective Binding by a Naphthalimide-Functionalized Amido-Amine Macrocycle

Amido-amine macrocycles
with two and four naphthalimide dyes were
designed to bind nucleoside monophosphates and oligonucleotides in
an aqueous buffered solution. Anion-templated synthesis was used to
direct the macrocyclization reaction to the [2+2] product, while high
dilution conditions favored the formation of the [4+4] macrocycle
with an unprecedented geometry, as revealed from the X-ray analysis.
The [2+2] product was found to exhibit a remarkable binding strength
and fluorescence response for cyclic guanosine monophosphate (cGMP)
in an aqueous solution. To our knowledge, this is the first synthetic
receptor for cGMP, which also demonstrates a high preference to bind
guanine-rich sequences accomplished by a strong fluorescence quenching.
The receptor conformation is very sensitive to the guest structure
in an aqueous solution, thus modeling the adaptive behavior of proteins.
The study of synthetic systems with a detectable conformational equilibrium
represents a great potential for understanding highly specific and
tightly regulated interactions in biological systems.