Sequence‐Controlled Peptoid Polymers: Bridging the Gap between Biology and Synthetic Polymers

Discovery of a Peptoid-Based Nanoparticle Platform for Therapeutic mRNA Delivery via Diverse Library Clustering and Structural Parametrization

“…Peptoids, or N-substituted alpha-amino acid oligomers, are a class of biomacromolecules structurally related to the commonly known peptides, but which incorporate side chain functionality on the amide nitrogen rather than α carbon, allowing for a significantly expanded set of monomer functionality, modular synthesis, and distinct structural properties. 25 Foundational work by Zuckermann demonstrated that this class of materials can be expediently synthesized in high yield and fidelity on a solid support using the submonomer approach wherein repeating cycles of acylation using bromoacetic acid and nucleophilic displacement by primary amines grow these materials in a stepwise, programmable fashion. 26−28 Peptoids have been successfully used in many applications including antibiofouling 29 and antibacterial agents, 30,31 drug delivery, 32 antifreeze additives in tissue storage, 33,34 and even as complexing agents for nucleic acids 35 or shielding lipids for LNPs, 36−38 but never as the ionizable component for mRNA delivery.…”

Sequence-Isomerism-Controlled Macromolecular Self-Assembly in Dendritic Rod-Like Molecules

“…Based on the precise recognition of the monomer sequence, genetic information can be encoded by merely four types of nucleobases in DNA . Built from 20 different types of l -α-amino acids, the diverse compositions and sequences of amino acid residues control the folding of proteins into precise tertiary structures, which further enable biochemical roles such as molecular recognition, metabolic reactions catalysis, and molecule transport …”

“…3 Built from 20 different types of L-αamino acids, the diverse compositions and sequences of amino acid residues control the folding of proteins into precise tertiary structures, which further enable biochemical roles such as molecular recognition, metabolic reactions catalysis, and molecule transport. 4 Inspired by Nature, the sequence of monomers has also been considered an essential element that influences the structures and properties of synthetic macromolecules, with great potential in applications of nanotechnology, 5,6 biomedicine, 7 and information storage. 8,9 Especially, driven by the desire and curiosity to obtain complex and exquisite nanostructures via macromolecular self-assembly, 10−12 the impact of the monomer sequence on macromolecular selfassembly has been attracting increasing interest.…”

Arylopeptoid oligomers functionalised by combinatorial or sequential on-resin click chemistry using a copper(i)–N-heterocyclic carbene catalyst

“…Toward this aim, N -substituted aminomethylbenzamide oligomers are particularly well adapted and represent particularly promising aromatic oligoamides. 3 They were named arylopeptoids 4 since their backbone can be considered as the peptoid ( N -substituted glycine oligomer) 5 backbone in which a phenyl group is inserted (Fig. 1).…”