Oral Presentation 8th Modern Solid Phase Peptide Synthesis & Its Applications Symposium 2022

Electrifying Peptide Synthesis (#1)

Lara R Malins 1
  1. Research School of Chemistry, Australian National University , Canberra, ACT, Australia

The structural diversity of peptide natural products extends well beyond the incorporation of canonical amino acids. The precise enzymatic editing of ribosomally-produced peptide sequences is one of Nature’s most powerful strategies for structural and functional diversification.1 Consequently, synthetic strategies for the late-stage modification of peptides are in exceedingly high demand as tools for accessing and improving on Nature’s templates to generate modified peptides as new therapies and functional materials.

This talk will highlight our recent efforts toward electrochemically-enabled peptide modifications.2-4 Despite the versatility and tunability of electroorganic chemistry, electrochemical transformations are underexplored in the context of late-stage peptide modifications. Inspired by seminal work from the 1980s,5 we have leveraged the power of anodic oxidation to facilitate the C-terminal modification of unprotected peptides.2,3 This methodology is exemplified in the synthesis of bioactive peptide natural products and related structural analogues. Given the compatibility of the method with conventional solid-phase peptide synthesis techniques, we envision that the electrochemical editing of peptide substrates will serve as a valuable addition to the toolbox of late-stage modifications.4

6205b560233a1-EPS2022_abstract.tiff

  1. Arnison, P. G. et al. Nat. Prod. Rep. 2013, 30, 108–160.
  2. Lin, Y.; Malins, L. R. Chem. Sci. 2020, 11, 10752–10758.
  3. Lin, Y.; Malins, L. R. J. Am. Chem. Soc. 2021, 143, 30, 11811–11819.
  4. Mackay, A. S.; Payne, R. J.; Malins, L. R. J. Am. Chem. Soc. 2022, 144, 23–41.
  5. Renaud, P.; Seebach, D. Angew. Chem. Int. Ed. 1986, 25, 843–844.