Patterned polypept(o)ide bottlebrush copolymers with orthogonal end groups for biofunctional interfaces

ChemRxiv

Abstract

Synergistic interactions between spatially clustered, chemically distinct ligands are central to many biolog-ical processes. Mimicking this complexity in synthetic systems requires precise spatial control over multi-ple orthogonally functionalized domains. Here, we report a modular strategy for the synthesis of poly-pept(o)ide bottlebrush copolymers with alternating surface functionalities. Orthogonally protected poly(L-lysine) backbone (tert-butoxycarbonyl and trifluoroacetyl) were prepared by sequential ring-opening polymerizations and used as macroinitiator. A sequence of “selective deprotection, sarcosine N-carboxyanhydride grafting-from, and end-group installation” yields brushes with alternating azide and secondary amine side chain termini, forming AB/ABA/ABAB patterns. The resulting bottlebrushes exhibit high grafting density (>86%) and tunable lengths (backbone DPn,bb = 80–132, side chain DPn,sc = 36–95), and behave as single, shape-persistent macromolecules (Rg/Rh ≈ 1.1 by multi-angle dynamic and static light scattering) in aqueous solution. Noteworthy, hydrophilic polysarcosine minimizes nonspecific interactions while keeping terminal groups accessible. Protease digestion of the peptide backbone cleanly releases two narrow pSar populations, confirming side chain uniformity and scaffold degradability. This platform pro-vides a general route to chemically patterned macromolecules and a foundation for future studies of syner-gistic ligand display, targeted biointerfaces, and adaptive nanomaterials.

Authors 5

1. Bonan Zhao Aachen

   Leiden University

   Affiliation as printed

   Leiden University

2. Christine Ilona Seidl Aachen

   Leiden University

   Affiliation as printed

   Leiden University

3. Rüdiger Berger

   Max Planck Institute for Polymer Research

   Affiliation as printed

   Max Planck Institute for Polymer Research

4. Lu Su Aachen

   Leiden University

   Affiliation as printed

   Leiden University

5. Matthias Barz Aachen

   Leiden University

   Affiliation as printed

   Leiden University