Solid-phase peptide synthesis using racemic amino acids yields stereorandomized peptides comprising all possible diastereomers as homogeneous, single-mass products that can be purified by HPLC. Here, we tested its compatibility with target binding peptides using Oncocin, a proline-rich AMP. Stereorandomization of up to nine C-terminal residues preserved ribosome binding and antibacterial effects including activities against drug-resistant bacteria and protected against serum degradation.
Our experiments show that stereorandomization can be compatible with target binding peptides and can help understand their mechanism of action.

This work was carried out in the group of Prof. Dr. Jean-Louis Reymond.

References:

• B. H. Gan^§, E. Bonvin^§, T. Paschoud^§, H. Personne, J. Reusser, X. Cai, R. Rauscher, T. Köhler, C. van Delden, N. Polacek, J.-L. Reymond^*;
  "Stereorandomized Oncocins with Preserved Ribosome Binding and Antibacterial Activity"
  J. Med. Chem., 2024, 67(21), 19448-19459; doi:10.1021/acs.jmedchem.4c01768.