Unmet Need: Study of the common DNA damage oxidative lesion Fapy∙dG has been extremely limited due to the lack of tools available to synthesize oligonucleotides containing this lesion.
Technical Details: Johns Hopkins researchers have developed a solid-phase synthetic method to prepare oligonucleotides containing N6-(2-Deoxy-α,β-D-erythropentofuranosyl)-2,6-diamino-4-hydroxy-5-formamidopyrimidine (Fapy•dG). Fapy•dG containing oligonucleotide synthesis is achieved by implementing a novel Fapy∙dG generation strategy that limits undesired isomerization of the molecule along with use of well-established solid-phase oligonucleotide synthesis reagents. This method is robust in enabling Fapy•dG containing oligonucleotide synthesis of comparable lengths to industry standards, and is compatible with the synthesis of additional formamidopyrimidines. Overall, this novel method will allow for more extensive study of Fapy•dG containing DNA lesions, their repair mechanisms, effect on replication and transcription in cells, and involvement in cancer development.
Value Proposition:
Looking for Partners to: Develop & commercialize the technology as a novel method to generate Fapy•dG containing oligonucleotides for the study of multiple cellular processes including cancer development.
Stage of Development: Oligonucleotide synthesis validated by MALDI-TOF MS and ESI-MS
Inventors: Marc M. Greenberg, Haozhe Yang
Patent Status: Pending
Publication(s): Chem. Eur. J. 2020, 26, 5441 – 5448