Sequence-controlled polymer

In nature, DNA, RNA, proteins and other macromolecules can also be recognized as sequence-controlled polymers for their well-ordered structural skeletons.

Through precise sequences of DNA, 20 amino acids are able to generate sequential peptide chains with three-dimensional structures by virtue of transcription and translation process.

[9] This technology called protein engineering is considered as the most promising biological polymerization method for synthesis of sequence-controlled polymers.

[1] One of the chemical polymerization methods is solid-phase synthesis, which can be used to synthesize peptides consisted of natural and non-natural amino acids.

The first reported example was the time-controlled sequential addition of highly-reactive N-substituted maleimides in the atom transfer radical polymerization of styrene, which led to programmed sequences of functional monomers.

[13] Other solutions include the use of intermediate purification steps to isolate the desired oligomer sequence in between subsequent reversible addition−fragmentation chain-transfer polymerization (RAFT-polymerizations).

Within those non-radical methods, azide-alkyne cycloaddition (also known as click reaction),[18] olefin metathesis[19] among others are utilized to construct sequence-controlled polymers.

One of the most significant character of sequence-controlled biosynthesis against other chemical synthetic methods is that the biomolecules (including DNA and RNA) can initiate their polymerization using highly programmed templates.

One successful example demonstrates that methacrylic acid (monomer) can be radically incorporated into a backbone featuring a recognizable cationic site (protonated primary amine pendant).

[24] Driven by this site-specific reaction, the sequence-controlled polymerization can be achieve by using a template adorned with differenrt recognizable pendants.

The property of sequence control make sequence-controlled polymers an ideal platform to install various kinds of pendants (like drugs, catalyst), whereby diverse functions and applications can be realized.

Fig 1. Synthetic rationale of sequence-controlled polymers. A and B shown here are two self-reacting monomers and one of which is pre-protected and can get deprotected thereafter to trigger the next addition. Based on selective AB reaction, the monomers can be added to the polymer chain in an ordered manner.
Fig 2. Schematic diagram of transcription-translation process in ribosome. Codon in mRNA and its specific recognization with tRNA ensure the ordered sequence of peptide. The peptide bonds are formed via amidation between amino group and ester group in two adjacent tRNAs, along with removal of the front tRNA and insertion of follow-up tRNA stepwise. This reduplicative cycle affords a sequence-controlled polymer (peptides). [ 5 ]
Fig 3. An example of click chemistry in synthesis of sequence-controlled polymers. (R refers to various kinds of functional moieties) [ 17 ]
Fig 4. An example of utilization of amine pendant as recognization site to direct site-specific addition of monomer [ 24 ]