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2. Nucleic acid

Numerous studies have shown that nucleic acids can be used as efficient therapeutic agents. An increasing number of these therapeutics are approved to treat a large range of diseases.

DNA and RNA can adopt a variety of three-dimensional structures. Indeed, single stranded molecules can form double stranded structures by folding over on itself, forming hairpins and pseudoknots stabilized by the intramolecular hydrogen bonds formed through complementary pairing of contiguous bases. These secondary structures also fold into 3-dimensional tertiary structures. In addition, particularly in RNA, unusual base-pairing can occur, including wobble base-pairs between guanine and uracil and Hoogsteen-type base-pairs between two purine nucleotides. They are less stable that standard Watson-Crick-type base-pairs but stabilize complex higher-order structure such as G-quadruplex.

Understanding DNA and RNA structure represents a major challenge. A panel of methods is required to better satisfy the analytical needs and to perform extensive structural characterization.
Infrared spectroscopy can be part of this panel and contribute to characterize the higher-order structure. It can indeed bring information related to:

  • The backbone conformation;
  • Base stacking and base pairing interactions;
  • The sugar conformation and puckering modes.

 

Our related case studies

 

References:

J.A. Kulkarni, D. Witzigmann, S.B. Thomson, S. Chen, B.R. Leavitt, P.R. Cullis, R. van der Meel, The current landscape of nucleic acid therapeutics, Nat. Nanotechnol. 16 2021, 630–643.

D.R. Whelan, K.R. Bambery, P. Heraud, M.J. Tobin, M. Diem, D. McNaughton, B.R. Wood, Monitoring the reversible B to A-like transition of DNA in eukaryotic cells using Fourier transform infrared spectroscopy, Nucleic Acids Res. 39 2011, 5439–5448.

M. Banyay, J. Sandbrink, R. Strömberg, A. Gräslund, Characterization of an RNA bulge structure by Fourier transform infrared spectroscopy, Biochem. Biophys. Res. Commun. 324 2004, 634–639

M. Banyay, M. Sarkar, A. Gräslund, A library of IR bands of nucleic acids in solution, Biophys. Chem. 104 2003, 477–488.

F. Geinguenaud, V. Militello, V. Arluison, Application of FTIR Spectroscopy to Analyze RNA Structure, Methods Mol. Biol. 2113 2020, 119–133.

M. Kloczewiak, J.M. Banks, L. Jin, M.L. Brader, A Biopharmaceutical Perspective on Higher-Order Structure and Thermal Stability of mRNA Vaccines, Mol. Pharm. 19 2022, 2022–2031.