Exploring Nucleic Acid Mimics: Can They Cross Bacterial Walls?

Nucleic acid mimics (NAMs) are promising antibacterial drugs, but do they actually cross the bacterial envelope? Scientists used computer simulations and experiments to find out. They studied how NAMs made of locked nucleic acid (LNA) and 2'-O-methyl (2'-OMe) residues move through lipid bilayers that mimic the bacterial outer membrane. These membranes were made of POPC or POPG phospholipids. Scientists found that NAMs prefer to form hydrogen bonds with anionic membranes over zwitterionic ones.They also discovered that NAMs face a lower energy barrier when crossing zwitterionic bilayers. However, they seem to prefer staying in anionic membranes. Experiments with liposomes showed slight partitioning, suggesting more research is needed. In the end, passive diffusion alone might not be enough for NAMs to cross the bacterial outer membrane.