skip to main content

Title: Synthetic approaches for copolymers containing nucleic acids and analogues: challenges and opportunities
Deep integration of nucleic acids with other classes of materials has become the basis of many useful technologies. Among these biohybrids, nucleic acid-containing copolymers have seen rapid development in both chemistry and applications. This review focuses on the various synthetic approaches for accessing nucleic acid–polymer biohybrids spanning post-polymerization conjugation, nucleic acids in polymerization, solid-phase synthesis, and nucleoside/nucleobase-functionalized polymers. We highlight the challenges associated with working with nucleic acids with each approach and the ingenuity of the solutions, with the hope of lowering the entry barrier and inspiring further investigations in this exciting area.
Authors:
; ;
Award ID(s):
2004947
Publication Date:
NSF-PAR ID:
10225738
Journal Name:
Polymer Chemistry
Volume:
12
Issue:
15
Page Range or eLocation-ID:
2193 to 2204
ISSN:
1759-9954
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract

    Upon sensing cytosolic- and/or viral double-stranded (ds)DNA, absent-in-melanoma-2 (AIM2)-like-receptors (ALRs) assemble into filamentous signaling platforms to initiate inflammatory responses. The versatile yet critical roles of ALRs in host innate defense are increasingly appreciated; however, the mechanisms by which AIM2 and its related IFI16 specifically recognize dsDNA over other nucleic acids remain poorly understood (i.e. single-stranded (ss)DNA, dsRNA, ssRNA and DNA:RNA hybrid). Here, we find that although AIM2 can interact with various nucleic acids, it preferentially binds to and assembles filaments faster on dsDNA in a duplex length-dependent manner. Moreover, AIM2 oligomers assembled on nucleic acids other than dsDNA not only display less ordered filamentous structures, but also fail to induce the polymerization of downstream ASC. Likewise, although showing broader nucleic acid selectivity than AIM2, IFI16 binds to and oligomerizes most readily on dsDNA in a duplex length-dependent manner. Nevertheless, IFI16 fails to form filaments on single-stranded nucleic acids and does not accelerate the polymerization of ASC regardless of bound nucleic acids. Together, we reveal that filament assembly is integral to nucleic acid distinction by ALRs.

  2. Nature encodes the information required for life in two fundamental biopolymers: nucleic acids and proteins. Peptide nucleic acid (PNA), a synthetic analog comprised of nucleobases arrayed along a pseudopeptide backbone, has the ability to combine the power of nucleic acids to encode information with the versatility of amino acids to encode structure and function. Historically, PNA has been perceived as a simple nucleic acid mimic having desirable properties such as high biostability and strong affinity for complementary nucleic acids. In this feature article, we aim to adjust this perception by highlighting the ability of PNA to act as a peptide mimic and showing the largely untapped potential to encode information in the amino acid sequence. First, we provide an introduction to PNA and discuss the use of conjugation to impart tunable properties to the biopolymer. Next, we describe the integration of functional groups directly into the PNA backbone to impart specific physical properties. Lastly, we highlight the use of these integrated amino acid side chains to encode peptide-like sequences in the PNA backbone, imparting novel activity and function and demonstrating the ability of PNA to simultaneously mimic both a peptide and a nucleic acid.
  3. Peptide nucleic acids (PNAs) are high-affinity synthetic nucleic acid analogs capable of hybridization with native nucleic acids. PNAs synthesized having amino acid sidechains installed at the γ-position along the backbone provide a template for a single biopolymer to simultaneously encode nucleic acid and amino acid sequences. Previously, we reported the development of “bilingual” PNAs through the synthesis of an amphiphilic sequence featuring separate blocks of hydrophobic and hydrophilic amino acid functional groups. These PNAs combined the sequence-specific binding activity of nucleic acids with the structural organization properties of peptides. Like other amphiphilic compounds, these γ-PNAs were observed to assemble spontaneously into micelle-like nanostructures in aqueous solutions and disassembly was induced through hybridization to a complementary sequence. Here, we explore whether assembly of these bilingual PNAs is possible by harnessing the nucleic acid code. Specifically, we designed an amphiphile-masking duplex system in which spontaneous amphiphile assembly is prevented through hybridization to a nucleic acid masking sequence. We show that the amphiphile is displaced upon introduction of a releasing sequence complementary to the masking sequence through toehold mediated displacement. Upon release, we observe that the amphiphile proceeds to assemble in a fashion consistent with our previously reported structures. Our approach represents amore »novel method for controlled stimuli-responsive assembly of PNA-based nanostructures.« less
  4. Abstract The helical structures of DNA and RNA were originally revealed by experimental data. Likewise, the development of programs for modeling these natural polymers was guided by known structures. These nucleic acid polymers represent only two members of a potentially vast class of polymers with similar structural features, but that differ from DNA and RNA in the backbone or nucleobases. Xeno nucleic acids (XNAs) incorporate alternative backbones that affect the conformational, chemical, and thermodynamic properties of XNAs. Given the vast chemical space of possible XNAs, computational modeling of alternative nucleic acids can accelerate the search for plausible nucleic acid analogs and guide their rational design. Additionally, a tool for the modeling of nucleic acids could help reveal what nucleic acid polymers may have existed before RNA in the early evolution of life. To aid the development of novel XNA polymers and the search for possible pre-RNA candidates, this article presents the proto-Nucleic Acid Builder (https://github.com/GT-NucleicAcids/pnab), an open-source program for modeling nucleic acid analogs with alternative backbones and nucleobases. The torsion-driven conformation search procedure implemented here predicts structures with good accuracy compared to experimental structures, and correctly demonstrates the correlation between the helical structure and the backbone conformation in DNA andmore »RNA.« less
  5. Nucleic acids are ubiquitous in biological samples and can be sensitively detected using nucleic acid amplification assays. To achieve highly accurate and reliable results, nucleic acid isolation and purification is often required and can limit the accessibility of these assays. Encapsulation of these workflows onto a single device may be achieved through fabrication methodologies featuring commercial three-dimensional (3D) printers. This study aims to characterize fused deposition modeling (FDM) filaments based on their compatibility with nucleic acid storage using quantitative polymerase chain reaction (qPCR). To study the adsorption of nucleic acids, storage vessels were fabricated using six common thermoplastics including: polylactic acid (PLA), nylon, acrylonitrile butadiene styrene (ABS), co-polyester (CPE), polycarbonate (PC), and polypropylene (PP). DNA adsorption of a short 98 base pair and a longer 830 base pair fragment to the walls of the vessel was shown to vary significantly among the polymer materials as well as the color varieties of the same polymer. PLA storage vessels were found to adsorb the least amount of the 98 base pair DNA after 12 hours of storage in 2.5 M NaCl TE buffer whereas the ABS and PC vessels adsorbed up to 97.2 ± 0.2% and 97.5 ± 0.2%. DNA adsorption couldmore »be reduced by decreasing the layer height of the 3D printed object, thereby increasing the functionality of the ABS storage vessel. Nylon was found to desorb qPCR inhibiting components into the stored solution which led to erroneous DNA quantification data from qPCR analysis.« less