Antimicrobial Peptoids

About

Peptide drugs have shown considerable promise as medicines, and investment in this area by the pharmaceutical industry continues to increase. Areas of significant interest lie in the use of stabilised or stapled α-helices, (multi)cyclic peptides and peptidomimetics, which include ‘peptoids’. However, many peptide drugs are readily broken down in the human body - presenting drug formulation and delivery challenges. Moreover, physical properties such as water-solubility and membrane-permeability remain highly problematic. Many drugs fail in development at the pre-clinical stage due to poor physical properties and many limitations remain in developing peptide-based drugs with suitable pharmaceutical properties e.g. membrane permeability, bioavailability and water solubility. Aqueous formulation of peptides can, therefore, be non-trivial and are often formulated with excipients, surfactants and co-solvents, which may result in adverse side effects. Therefore, there is a need to improve peptidic drugs due to their inherently unfavorable pharmacokinetic properties e.g. stability, membrane permeability, bioavailability and water solubility. Peptoids are an emerging class of therapeutic agent, which are structurally very similar to peptides but have a superior proteolytic stability in vivo when compared with standard peptide-based drugs. Peptoids are an emerging class of therapeutic agent, which are structurally very similar to peptides but have a superior proteolytic stability in vivo when compared with standard peptide-based drugs. Peptoids that contain ‘lysine’ type side chains are routinely seen in the literature. Some research groups have sought to improve the biological activity of peptoids by replacing the ‘lysine’ residues with ‘arginine’ analogues. In part this change has been probed due to the fact that arginine-rich cell-penetrating peptides have been shown to have a high potential to deliver drugs into cultured cells. Recent work in the area has shown that guanidine containing peptoids translocate into the cell quicker than peptoids that only contain “lysine” (amine) type side chains.