A simple solid-phase synthesis of the ubiquitous bacterial signaling molecule, c-di-GMP and analogues

摘要

Cyclic-di-guanylate (c-di-GMP) has emerged as a general and important signaling molecule uniquely present in bacteria: herein we provide a simple solid-phase synthesis of c-di-GMP using an automated DNA synthesizer for the majority of the synthesis. Biofilm-causing bacteria are responsible for the majority (60-80%) of hospital-acquired microbial infections and are therefore of great medical interest. The biofilm environment increases the opportunity for gene transfer between bacteria thereby aiding bacterial resistance to conventional antibiotics. Biofilms also form a protective barrier for bacteria and are extremely difficult to treat because conventional antibiotics fail to penetrate the biofilm matrix. Therefore, suppressing biofilm synthesis with small molecules should make bacteria more susceptible to current antibiotics. Despite the great potential of biofilm-formation inhibitors, there is a paucity of small molecules that can inhibit biofilm synthesis. This is probably because the molecular mechanisms that underlie biofilm development have been poorly understood.