Fig. 1. Cationic depsipeptides and polyesters are generated in dry-down reactions.

Depsipeptide and polyester mixtures used in this study were generated via dry-down reactions, in the absence of condensing agents, from binary mixtures of a α-amino acids and b α-hydroxy acids. Cationic side chain moieties are blue. c Scheme showing some potential products of a dry-down reaction of the cationic α-hydroxy acid monomer hah. The major species observed by ¹H-NMR were acylated at the α-hydroxy position and free at the ε-amine position, corresponding to linear oligomers having a backbone topology similar to biological proteins, but with ester bonds in place of amide bonds. d ¹H-NMR spectrum of the product mixture resulting from a hah dry-down at 85 °C for 7 days. Integration of the free α-proton indicated that 56% of hah was incorporated into oligomers. The downfield ε-protons at ~3.1 ppm (12% by integration) likely correspond to ε-amidation, in analogy to chemical shift patterns observed upon ε-amidation of Lys in dry-down reactions³⁹. Some resonances corresponding to acylated α-species are obscured by the water peak and are not shown, but can be observed by COSY analysis (Supplementary Fig. 8). e Positive-mode ESI-MS spectra showing the production of cationic polyesters via dry-down reaction of hah at 85 °C for 7 days. Labeled species correspond to [M + H]⁺ ions.