An Unnatural Biopolymer

TLDR

Unnatural polymers offer new frameworks for drug development and for probing protein and peptide folding theories. The authors synthesized high‑efficiency oligocarbamates from N‑protected p‑nitrophenyl carbonate monomers, generated a spatially defined library via photochemical methods, and screened the compounds for monoclonal antibody binding. The developed solid‑phase synthesis produces an unnatural biopolymer with >99 % coupling efficiency, and the high‑affinity ligands derived from it exhibit strong inhibition, favorable partitioning, and proteolytic stability.

Abstract

A highly efficient method has been developed for the solid-phase synthesis of an "unnatural biopolymer" consisting of chiral aminocarbonate monomers linked via a carbamate backbone. Oligocarbamates were synthesized from N -protected p -nitrophenyl carbonate monomers, substituted with a variety of side chains, with greater than 99 percent overall coupling efficiencies per step. A spatially defined library of oligocarbamates was generated by using photochemical methods and screened for binding affinity to a monoclonal antibody. A number of high-affinity ligands were then synthesized and analyzed in solution with respect to their inhibition concentration values, water/octanol partitioning coefficients, and proteolytic stability. These and other unnatural polymers may provide new frameworks for drug development and for testing theories of protein and peptide folding and structure.