Precision Polymers: Monodisperse, Monomer‐Sequence‐Defined Segments to Target Future Demands of Polymers in Medicine

Abstract The established technology platforms of solid‐phase‐supported oligopeptide and oligonucleotide synthesis can be expanded to access fully synthetic macromolecules, preserving both the monodisperse character and the defined monomer sequence. Precision polymers are sequentially assembled from a library of functional building blocks, enabling one to program interaction capabilities or generate functions by sequence‐specific positioning of functionalities. Examples are provided, showing that these monodisperse macromolecules can be conjugated to oligonucleotides, oligopeptides, or poly(ethylene glycol)s. The resulting model systems can contribute to the understanding of complex biomedical‐related processes. Due to the absence of chemical and molecular‐weight distributions in these multifunctional segments, exact correlation of the monomer sequence and (bio)properties is attainable. This is demonstrated by the design of carrier systems that exhibit fine‐tuned interactions with plasmid DNA, actively controlling important steps in DNA delivery and transfection, such as polyplex formation, DNA compression, and release of the cargo.