For an organism to survive, it must sense its environment and coordinate metabolism to a changing environment. In bacteria, cyclic diguanylate (c-di-GMP) is a universal second messenger that is synthesized in the cytosol, in response to a changing bacterial environment, to regulate bacterial physiology. C-di-GMP has been shown to regulate biofilm formation as well as virulence gene expression in a variety of bacteria. Analogs of c-di-GMP have the potential to be used as chemical probes to study c-di-GMP signaling and could even become drug leads for the development of anti-biofilm compounds to treat persistent bacterial infections. Herein we report the synthesis and biophysical studies of a series of c-di-GMP analogs, which have both phosphate and sugar moieties simultaneously modified. We used computational methods to predict the relative orientation of the guanine nucleobases in c-di-GMP and analogs. DOSY NMR was used to characterize the aggregation states of the c-di-GMP and analogs. Binding studies with various c-di-GMP effector molecules (both proteins and RNAs) revealed that conservative modifications to the phosphate and 2'-positions of c-di-GMP dramatically affected aggregative behavior and binding properties to effector molecules.

Polymorphism and binding studies of c-di-GMP analogs

246th National Meeting (2013)

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