TOWARDS THE DESIGN OF EFFECTIVE ANTIMICROBIAL AGENTS

Pathogenic infections represent a persistent threat to human health. The rapid development of resistance to drug therapies creates a continuing need for developing new anti-infective agents. Host-Defense Peptides (HDPs) represent a potential source of inspiration for development of new antibacterial agents. The broad molecular diversity among HDPs suggests that their prokaryotic-selective activity is not tightly coupled to specific features of amino acid sequence or peptide conformation. This situation has inspired the development of several families of sequence-random hydrophobic-cationic co-polymers that display antibacterial behavior with varying levels of hemolytic activity. We employed solid-phase synthesis in an unconventional way to generate peptide mixtures that contain one type of hydrophobic residue and one type of cationic residue. Each mixture was random in terms of sequence, but highly controlled in terms of chain length and stereochemistry. Analysis of the antibacterial and hemolytic properties of these mixtures revealed that selective antibacterial activity can be achieved with heterochiral binary mixtures but not homochiral binary mixtures (1).

Surface microbial attachment reveal to biofilm formation. Biofilm can be defined as structured aggregation of surface-attached microorganisms encased in an extracellular matrix. Bacterial cells within biofilms are much less susceptible to conventional antibiotics treatment than are bacterial cells in a planktonic state hence; it is very challenging to target them. According to our findings we showed that our random peptide mixtures were able to prevent biofilm formation and more challenging even to eradicate mature biofilm. Our random peptides mixtures may be used as lead antimicrobial agents for many applications.

1. Hayouka, Z. Chakraborty, S. Liu, R. Gellman, H.S. J. Am. Chem. Soc. 2013, 135(32):11748-5.