This is the recording of the talk given by Anna Codina during the TIDES Europe 2023 in Amsterdam.
The wealth of structural information that accompanies NMR spectroscopy has made it instrumental for traditional small molecules medicinal and analytical chemistry support. Perhaps less well known is its ability to characterise peptides and oligonucleotides (TIDES) efficiently and with such a level of detail (atomic resolution). This talk demonstrates its power with examples covering TIDES structure-based drug design [1,2], similarity assessment [3], characterisation [4], secondary and tertiary structure, quantification and phosphorothioate chirality [5,6]
1. Haxholm GW, Petersen BO, Malmstrøm J. Higher-Order Structure Characterization of Pharmaceutical Proteins by 2D Nuclear Magnetic Resonance Methyl Fingerprinting. J Pharm Sci. 2019;108(9):3029-3035. https://doi.org/10.1016/j.xphs.2019.04.032
2. Gelenter MD, Smith KJ, Liao SY. et al. The peptide hormone glucagon forms amyloid fibrils with two coexisting β-strand conformations. Nat Struct Mol Biol. 2019;26:592–598. https://doi.org/10.1038/s41594-019-0238-6
3. Becette, OB, Marino, JP & Brinson, RG. Structural Fingerprinting of Antisense Oligonucleotide Therapeutics by Solution NMR Spectroscopy. Pharm Res. 2023;40:1373–1382. https://doi.org/10.1007/s11095-022-03403-x
4. https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_212194.pdf, accessed 15Oct23
5. Jahns H, Taneja N, Willoughby JLS, et al. Chirality matters: stereo-defined phosphorothioate linkages at the termini of small interfering RNAs improve pharmacology in vivo. Nucleic Acids Res. https://doi.org/10.1093/nar/gkab54
6. Genna V, Iglesias-Fernández J, Reyes-Fraile L, et al. Controlled sulfur-based engineering confers mouldability to phosphorothioate antisense oligonucleotides. Nucleic Acids Res. 2023;51(10):4713-4725. https://doi.org/10.1093/nar/gkad309
Wednesday 1 November 2023, 07:30 CET
Dr. Anna Codina
Director Pharmaceutical Business Unit, Bruker BioSpin