C5-pyrimidine-functionalized morpholino oligonucleotides exhibit differential binding affinity, target specificity and lipophilicity.
Arnab DasAtanu GhoshSurajit SinhaPublished in: Organic & biomolecular chemistry (2023)
C5-substituted uridine and cytidine morpholino chlorophosphoramidate monomers were synthesized and incorporated into a 12-mer Phosphorodiamidate Morpholino Oligonucleotide (PMO) using semi-automated solid phase synthesis. PMOs with most of the tested pyrimidine C5-substitutions have significantly increased thermal stability when bound to the complementary RNA strand relative to the PMO. They exhibit higher binding with RNA than DNA. CD-spectra show B-type helical conformation of duplexes. HPLC analysis indicates their greater lipophilicity compared to regular PMOs. These chemical modifications have significant potential towards the development of better antisense technologies.
Keyphrases
- nucleic acid
- ms ms
- machine learning
- dna binding
- deep learning
- simultaneous determination
- high throughput
- circulating tumor
- mass spectrometry
- molecular docking
- high performance liquid chromatography
- quantum dots
- single molecule
- cell free
- molecular dynamics simulations
- solid phase extraction
- human health
- high resolution
- molecularly imprinted