Proteins and there complex structural diversity are fundamental to life. Despite making significant inroads in to protein mimetics, synthetic approaches still lack the capability to replicate the intricacy of natural proteins when considering sequence-specificity at high molecular weight. At the same time, poly(N-substituted glycine’s) “peptoids“, have gained traction as versatile synthetic peptidomimetic materials that can exhibit remarkable sequence specific bioactivity and self-assembly or secondary structure-forming properties. Motivated by recent advances in N-thiocarboxyanhydride (NTA) polymerization that is enabling preparation of polypeptoids (and polypeptides) through ambient reaction conditions, we now report our investigation of combining N-substituted glycine NTA (NNTA) polymerization with sub-monomer ‘solid-phase synthesis’ (SPS). The goal is convenient, ambient preparation of high molecular weight peptoid block-copolymers possessing sequence specific designs. Prepared entirely in situ without the use of fragment condensation or post synthesis modification/purification steps, we demonstrate NNTA polymerization initiated from solid phase resin, achieving low polydispersity indices (PDI) of 1.1-1.2. Additionally we  exhibit for the first time on-resin NNTA initiation from SPS peptoid sequences and achieve multiblock co-polymer designs. We also present our initial findings in demonstrating bioactivity of our NNTA-SPS peptoids by incorporating antimicrobial sequences. The convenience of our procedure and narrow chain length distributions demonstrated point to a highly promising approach that combines the advantages of solution polymerization and solid phase synthesis for protein mimicry.

Benchtop preparation of block copolymers: Developing sequence specific design at high molecular weight

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.