Recent Progress Toward the Templated Synthesis and Directed Evolution of Sequence-Defined Synthetic Polymers

Abstract

Biological polymers such as nucleic acids and proteins are ubiquitous in living systems, but their ability to address problems beyond those found in nature is constrained by factors such as chemical or biological instability, limited building-block functionality, bioavailability, and immunogenicity. In principle, sequence-defined synthetic polymers based on nonbiological monomers and backbones might overcome these constraints; however, identifying the sequence of a synthetic polymer that possesses a specific desired functional property remains a major challenge. Molecular evolution can rapidly generate functional polymers but requires a means of translating amplifiable templates such as nucleic acids into the polymer being evolved. This review covers recent advances in the enzymatic and nonenzymatic templated polymerization of nonnatural polymers and their potential applications in the directed evolution of sequence-defined synthetic polymers.

Evolution of functional nucleic acids in the presence of nonheritable backbone heterogeneity

“…However, the laboratory generation and amplification of such mosaic nucleic acid pools would require mutant DNA or RNA polymerase that could incorporate such nucleotides into polymers and transcribe them back into RNA or DNA. Some naturally occurring error-prone or bypass DNA polymerases as well as artificially evolved mutant polymerases show a remarkable ability to incorporate nucleotides with sugar modifications into polymers (46,47). Such polymerases may enable the identification of additional types of structural variation that are tolerable in the evolution of functional molecules.…”

Sequence-regulated vinyl copolymers by metal-catalysed step-growth radical polymerization

“…For this purpose, various synthetic approaches have been developed, such as Merrifi eld ' s solid-phase synthesis and enzymatic or non-enzymatic template polymerization, which are used for the synthesis of oligopeptides and oligonucleotides from natural or non-natural building blocks and for producing non-natural oligoamides, oligoesters, oligoureas, oligocarbamates and oligosaccharides 1 -10 . Th ese are all condensation polymers consisting of heteroatom-containing main-chain linkages, such as amide, ester, ether and so on, and prepared by successive stepwise condensation reactions, which can be automated sometimes 2,3 .…”

Engineered DNA Polymerases in Biotechnology

“…[75] These artificial biopolymers could overcome current limitations such as instability, limited functional groups, bioavailability and immunogenicity. [71] To conclude, engineered DNA polymerases already are and will be the workhorses in many biotechnological applications in the future, which is why this growing field of research is attractive to both industry and academia alike.…”

“…[68] First examples show that DNA polymerases can indeed tolerate artificial amino acids without the significant loss of activity. [69] Future goals could be efficient enzymatic production and improved amplification of unnatural biopolymers [70,71] such as l-DNA, peptide nucleic acids (PNA), [72] locked nucleic acids (LNA), [73] glycol nucleic acids (GNA), [74] and threose nucleic acids (TNA). [75] These artificial biopolymers could overcome current limitations such as instability, limited functional groups, bioavailability and immunogenicity.…”