Stanford Advisors


All Publications


  • A SMUG1 Inhibitor Modulates the Excision of Pyrimidine DNA Damage ACS MEDICINAL CHEMISTRY LETTERS Thacker, P. S., Gao, Y., McPherson, L., Lee, A., Averill, A. M., Pratihar, S., Doublie, S., Ford, J. M., Kool, E. T. 2026
  • RNA 2'-OH modification with stable reagents enabled by nucleophilic catalysis. RSC advances Kool, E. T., Pratihar, S., Thacker, P. S., Banerjee, D., Kim, M. J., Shioi, R. 2025; 15 (43): 35749-35755

    Abstract

    RNA modification at 2'-OH has typically required highly reactive acylating species that exhibit short half-lives in water, challenging purification, and limiting shelf lives. Here, we investigate the use of more stable species as electrophilic reagents, employing nucleophilic catalysis to promote reactions. The results show that multiple previously unreported electrophiles can react in high stoichiometric yields with RNA under appropriate catalysis. Most notably, aryl esters can transfer acyl groups to RNA in one hour, but are stable for months even in pure water. The results expand the functional chemotypes of RNA-reactive species, and identify reagent classes with improved stability and selectivity.

    View details for DOI 10.1039/d5ra06314k

    View details for PubMedID 41018161

    View details for PubMedCentralID PMC12466920

  • Sequence-Specific Installation of Aryl Groups in RNA via DNA-Catalyst Conjugates. Angewandte Chemie (International ed. in English) Pratihar, S., Zhong, W., Feng, S., Chatterjee, S., Kool, E. T. 2025: e202515681

    Abstract

    Installing functional groups at specific sites in existing RNA molecules remains a challenge for modification, labeling, and therapeutic strategies. Here, we describe the use of DNA oligonucleotides carrying a catalytic amine group to effect the aqueous SNAr arylation of 2'-OH groups at sequence-complementary sites in RNAs. Chloro-pyrimidine electrophiles are shown to react with amino-DNA conjugates, resulting in a proposed transient ammonium aryl intermediate that can react with RNA near the DNA binding site, delivering the heterocycle to the RNA in high yields. In a test of utility, we construct an aryl electrophile carrying an azide group, and apply this strategy to fluorescently label messenger RNAs locally at the polyA tail. We also employ the approach to direct in vitro arylation in the coding region of a messenger RNA, knocking down protein expression selectively in the presence of another coding RNA. This sequence-directed catalytic strategy enables multiple applications in RNA labeling and modification.

    View details for DOI 10.1002/anie.202515681

    View details for PubMedID 40988407