title: Endo-S-c-di-GMP analogues-polymorphism and binding studies with class I riboswitch.
abstract: C-di-GMP, a cyclic guanine dinucleotide, has been shown to regulate biofilm formation as well as virulence gene expression in a variety of bacteria. Analogues 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. Herein we report the synthesis and biophysical studies of a series of c-di-GMP analogues, which have both phosphate and sugar moieties simultaneously modified (called endo-S-c-di-GMP analogues). We used computational methods to predict the relative orientation of the guanine nucleobases in c-di-GMP and analogues. DOSY NMR of the endo-S-c-di-GMP series showed that the polymorphism of c-di-GMP can be tuned with conservative modifications to the phosphate and sugar moieties (conformational steering). Binding studies with Vc2 RNA (a class I c-di-GMP riboswitch) revealed that conservative modifications to the phosphate and 2'-positions of c-di-GMP dramatically affected binding to class I riboswitch.
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.forename: David A
authors.initials: DA
authors.lastname: Sayre
authors.forename: Jingxin
authors.initials: J
authors.lastname: Wang
authors.forename: Nirmal
authors.initials: N
authors.lastname: Pahadi
authors.forename: Herman O
authors.initials: HO
authors.lastname: Sintim
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D003198:Computer Simulation; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D004058:Diffusion; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010084:Oxidation-Reduction; D058928:Riboswitch; D060327:Solid-Phase Synthesis Techniques; D013816:Thermodynamics
chemical_list: D058928:Riboswitch; D006152:Cyclic GMP