"Amphipathic Dimers: A New Class of Antibiotics"

Recently, the number of bacterial strains that have acquired resistance to antibiotics through either genetic mutations or genetic exchange has risen at an alarming rate.  As a result,many antibiotics that were capable of treating bacterial infections in the past are currently not viable, giving rise to the need for a new class of drugs.  In higher organisms it is now well known that protection relies on the synthesis and delivery of gene-encoded antimicrobial peptides.  Such antimicrobial substances have been found to exist within the granules of phagocytic cells in both vertebrates and invertebrates as well as in the seeds and leaves of plants, serving as key players in innate immunity.  Targets susceptible to attack by the innate defense system include both Gram-positive and Gram-negative bacteria, yeasts, fungi, and even some viruses and protozoa.  Of the AMPs that have been characterized, we are focusing on a small class of aromatic dipeptides that have been isolated from dipteran larvae.  One of its members includes p-hydroxycinnamaldehyde, a small molecule that demonstrates antimicrobial activity by means of a mechanism that is not well understood.  Using this molecule as a model, we are in the process of developing small amphipathic dimers as a potentially new class of antibiotics.