The thiol-Michael addition of ethanethiol to ethyl acrylate, methyl vinylsulfone and maleimide initiated by ethyl-, diethyl-, triethylamine and triethylphosphine in tetrahydrofuran (THF) is investigated at room temperature.

Functional sequences of precision polymers based on thiolactone/Michael chemistry are identified from a large one‐bead one‐compound library. Single‐bead readout by MALDI‐TOF MS/MS identifies sequences that host m‐THPC that is a second generation photo‐sensitizer drug. The corresponding Tla/Michael‐PEG conjugates make m‐THPC available in solution and drug payload as well as drug release kinetics can be fine‐tuned by the precision segment.

Functional sequences of monodisperse, sequence‐defined oligo(amide‐urethane)s are designed based on a peptide sequence as blueprint. The translation of a discrete side‐chain functionality sequence from a known peptide‐based solubilizer of the photosensitizer meta‐tetra(hydroxyphenyl)‐chlorin, into a non‐peptidic precision polymer backbone is demonstrated. The resulting peptidomimetic precision polymers retain the functions of the parent peptide sequence, showing analogues sensitivity toward single monomer mutations/exchanges and even exceeding the parent peptide equivalent by reaching up to 69% higher payload capacities and more favored release kinetics.

A straightforward access route to multifunctional block copolymers, combining a poly(ethylene glycol) (PEG) block and a monodisperse segment with discrete monomer sequence based on thiolactone chemistry, is described. Exploiting an inverse conjugation strategy on a PEG preloaded poly(styrene) synthesis resin enables the convenient introduction of a predefined PEG-block at the α-terminus of thiolactone-based sequence-defined oligomers. Reaction conditions for the stepwise, submonomer synthesis at polar solid supports are optimized, using sequential synthesis on a model resin that enables to isolate and determine the purity of the oligomer segments by liquid chromatography-electrospray ionization mass spectrometry analysis. The reaction conditions are used to synthesize PEGylated 5mer precision polymers with defined monomer sequence in good yields and high purity to offer an interesting platform of macromolecules with potential for biomedical applications.