Reading Polymers: Sequencing of Natural and Synthetic Macromolecules

Abstract

The sequencing of biopolymers such as proteins and DNA is among the most significant scientific achievements of the 20th century. Indeed, modern chemical methods for sequence analysis allow reading and understanding the codes of life. Thus, sequencing methods currently play a major role in applications as diverse as genomics, gene therapy, biotechnology, and data storage. However, in terms of fundamental science, sequencing is not really a question of molecular biology but rather a more general topic in macromolecular chemistry. Broadly speaking, it can be defined as the analysis of comonomer sequences in copolymers. However, relatively different approaches have been used in the past to study monomer sequences in biological and manmade polymers. Yet, these "cultural" differences are slowly fading away with the recent development of synthetic sequence-controlled polymers. In this context, the aim of this Minireview is to present an overview of the tools that are currently available for sequence analysis in macromolecular science.

Coding Macromolecules: Inputting Information in Polymers Using Monomer-Based Alphabets

“…80−82 The differences between sequencing and sequence analysis were discussed in details in a recent review. 67 The readers may refer to that text for an overview on these topics. Sequencing methodologies have been primarily developed for the analysis of biopolymers such as proteins and DNA.…”

“…However, these available sequencing methodologies have been rarely used for characterizing non-natural polymers. 67 Some of these methodologies rely on biological concepts (e.g., DNA amplification, polymerase-based sequencing, enzymatic cleavage) and cannot be applied to all polymers. However, some other are more universal.…”

“…Preliminary measurements made with sequence-coded polyphosphates (Figure 2a) and oligo(triazole amide)s (Figure 2b) indicated that the MS/ MS fragmentation pathways of these polymers is more complex than the one found for oligo(alkoxyamine amide)s. However, other sequencing techniques can be considered for these polymers. 67 For example, water-soluble sequence-coded polyphosphates are interesting analytes for nanopore sequencing. In this technique, the polymer is analyzed in a pore, which can be biological or synthetic.…”

Recent developments in the synthesis of sequence controlled polymers

“…Sequence specificity is achieved through either copolymerization of XaX and YbY type monomers (alternatdoi: 10.1007/s11426-015- ing copolymer) or homopolymerization of XabY type sequence built-in monomers. An extensive review on sequence control in traditional condensation polymerization was published by Ueda [23].…”

“…Nevertheless, the monomer sequence control is a great challenge and remains as a "Holy Grail" in polymer synthesis [1][2][3]. Recently, there are increasing efforts to mimic bio-system in the synthesis of sequence controlled polymers [4][5][6][7][8] and study their particular property and application, such as single chain folding [9] and information storage [10][11][12].…”