Synthesis and characterization of C8 analogs of c-di-GMP.

We have synthesized five analogs of c-di-GMP with different substituents at the guanine C8 position, to study their effects on the metal-dependent polymorphism we had previously demonstrated for the parent compound. Of these, only the K(+) salt of c-di-Br-GMP, 2, forms higher order complexes, predominantly two different syn octamolecular ones. Its Na(+) salt, as well as both the K(+) and Na(+) salts of c-di-thio-GMP, 3, c-di-methylthio-GMP, 4, c-di-phenyl-GMP, 5, and c-di-acetylphenyl-GMP, 6, all form primarily a syn bimolecular structure.