Chain-Growth Synthesis of Sequence-Defined Native Polypeptides via Traceless Cascade Polymerization
Year: 2026
Type: preprint
Abstract: Despite sharing a common macromolecular foundation, synthetic polymers and sequencedefined biomacromolecules have historically evolved along distinct trajectories. Extending the principles of polymerization beyond synthetic materials to nature’s own sequence-defined polymers therefore remains a longstanding challenge. Here we address this challenge by developing a controlled chain-growth polymerization strategy for the synthesis of repetitive sequence-defined native polypeptides. A traceless peri-naphthalene cascade relays the propagating chain end while connecting peptide segments exclusively through native peptide bonds. The resulting synthetic polypeptides reproduce the sequence-dependent biophysical behavior of recombinant analogues while accommodating non-canonical α-, β-, and ᴅ-amino acids. This work fundamentally expands the molecular complexity accessible through controlled polymerization, placing sequence-defined native biomacromolecules within the same chain-growth paradigm as synthetic polymers.
Source: ChemRxiv
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7204991629