Poster Presentation 7th Modern Solid Phase Peptide Synthesis & Its Applications Symposium 2019

Controlling the assembly of D/L cyclic peptides through a linear scaffold (#110)

Amanda Handrisanto 1 , Mitchell R Silk 1 , David Manallack 1 , Philip E Thompson 1 , David K Chalmers 1
  1. Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Melbourne, VIC, Australia

Peptide nanotubes that assemble by H-bonded cyclic D/L peptides (DLCPs) have a great potential for construction of diverse nanomaterials. The rigid geometry and the tunability of the chemistry make them an intriguing building block for the rational design of nano-structured materials.1 They have potential applications as drug-delivery vehicles or synthetic membrane penetrating protein/ion-channels. However, DLCPs have some limitations that could hinder their use as a functional nanomaterials or synthetic ion channels. DLCPS can have low aqueous solubility and it is difficult to control their self-assembly process resulting in nanotubes with indeterminate lengths. Prior research within our group has presented a potential solution to control the length of peptide nanorods through coupling of amino acid side-chains using copper-activated azide-alkyne cycloaddition and disulfide bonds.2 This project presents another potential solution to the control of length of peptide nanorods, by tethering cyclic peptides to a linear anchor through formation of triazole, creating molecules known as the “Rack CP”. To date, a series of Rack CPs differing in their length have been synthesised, providing a potential nanomaterials with ease of tunability and further functionalisation. These Rack CPs are a starting point in generating a new class of DLCPs.

  1. Ghadiri et al., Nature, 1993, 366, 324-327.
  2. Silk et al., Angewandte Chemie, 2019, 131, 606-611.