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.

Precision Polymers—Modern Tools to Understand and Program Macromolecular Interactions

“…The synthesis of macromolecules, exhibiting a high level of control, which is currently difficult to achieve with established polymerization processes would lead to precisely defined polymer systems, referred to as ''Precision Polymers.'' [6] Synthesis of Monodisperse Polymers…”

Tailored Polymer Microstructures Prepared by Atom Transfer Radical Copolymerization of Styrene and N‐substituted Maleimides

“…[1][2][3][4][5][6][7][8][9] The core idea of this new trend is to progress beyond the current state of the art in polymer synthesis and, in particular, beyond the control of macromolecular architecture. For instance, one of the primary goals of the field of precision macromolecular chemistry is to control monomer sequence distribution in synthetic polymer chains.…”

“…[11,13] Iterative synthetic approaches (e.g., solid-phase synthesis) allow the design of short sequence-defined oligomers; however these technically demanding syntheses remain unfortunately marginal in synthetic polymer science. [4,[13][14][15] Besides, one-pot polymerization processes such as step-growth or chain-growth polymerizations offer very limited options for controlling macromolecular sequences. [11] Indeed, in these conventional synthetic approaches, polymer chains are assembled in a concentrated ''soup'' of comonomers, and thus statistics govern the copolymerization processes.…”

Nucleic Acid Carriers Based on Precise Polymer Conjugates

“…This polyamidoamine-block-PEG with a single disulfide moiety was synthesized by the selective positioning of a cysteamine (Cya) into the polyamine backbone (PEG 60 ÀLys(SucÀCyaÀLys 2 )À (SucÀDampÀLys 2 ) 4 ). 75 The disulfide bonds of this linear polymer can be degraded in the intracellular reductive environment of cells. Gel electrophoresis revealed the formation of stable pDNAÀpolyplexes with polyplex size around 160 nm and a zeta potential of 0 due to the steric shielding effects of PEG.…”