The structural diversity of artificial genetic polymers

Abstract

Synthetic genetics is a subdiscipline of synthetic biology that aims to develop artificial genetic polymers (also referred to as xeno-nucleic acids or XNAs) that can replicate in vitro and eventually in model cellular organisms. This field of science combines organic chemistry with polymerase engineering to create alternative forms of DNA that can store genetic information and evolve in response to external stimuli. Practitioners of synthetic genetics postulate that XNA could be used to safeguard synthetic biology organisms by storing genetic information in orthogonal chromosomes. XNA polymers are also under active investigation as a source of nuclease resistant affinity reagents (aptamers) and catalysts (xenozymes) with practical applications in disease diagnosis and treatment. In this review, we provide a structural perspective on known antiparallel duplex structures in which at least one strand of the Watson–Crick duplex is composed entirely of XNA. Currently, only a handful of XNA structures have been archived in the Protein Data Bank as compared to the more than 100 000 structures that are now available. Given the growing interest in xenobiology projects, we chose to compare the structural features of XNA polymers and discuss their potential to access new regions of nucleic acid fold space.

Structural Insights into Conformation Differences between DNA/TNA and RNA/TNA Chimeric Duplexes

“…This observation is consistent with previous analyses performed on mixed-sequence TNA/RNA and TNA/DNA hetero- and homoduplexes. [1a] Moreover, the T m values observed by UV spectroscopy melting are partially reflected by the thermodynamic parameters obtained by isothermal titration calorimetry (ITC, Table 1, and Figure S3). The ITC results indicate that all duplexes have similar association stabilities with an average ΔG of −43 ± 3 kJ/mol.…”

“…[1] Despite a backbone repeat unit that is one atom shorter than that found in DNA and RNA, TNA is capable of adopting stable Watson-Crick duplex structures with itself and with complementary strands of DNA and RNA. [1a, 2] The ability to exchange genetic information with RNA has raised significant interest in TNA as an RNA progenitor during the early stages of life on Earth. [3] …”

The expanding world of DNA and RNA

“…While too few studies have focused on if and how nucleobase modifications allow access to an increased range of function, comparative analysis of SELEX experiments suggest that they increase the likelihood of aptamer identification, and structural analyses suggest that they do so by allowing oligonucleotides to adopt a broader range of conformations and structural motifs [21••,45,46]. Moreover, the observation of similar structural motifs when hydrophobic aromatic moieties are introduced, either via modification (SOMAmers) or as the nucleobases of UBPs, suggests that common themes, and perhaps even rules that will facilitate design, are possible.…”

Xeno-Nukleik Asitler ve XNA Dunyasi

“…XNA'lar kendisiyle XNA:XNA, doğal DNA/RNA ile XNA:DNA, XNA:RNA şeklinde sekonder (çift sarmal) yapı oluşturabilmektedir (12). FANA (Fluoroarabino nükleik asit), ilk kez kendisini kalıp olarak kullanıp kopyasını çıkaran XNA tipidir (11).…”