WARF: P05116US

Synthetic Cofactor Analogs of S-Adenosylmethionine as Ligatable Probes of Biological Methylation


Scott Rajski, Lindsay Comstock, Rachel Weller

The Wisconsin Alumni Research Foundation (WARF) is seeking commercial partners interested in developing compounds and methods for specifically labeling the substrates of SAM-dependent methyltransferases.
OVERVIEWMethylation of nucleic acids and proteins is necessary for normal development and cellular viability of organisms. The most important cofactor in substrate methylation is S-adenosyl-L-methionine (SAM), with SAM-dependent methylation of nucleic acids and proteins playing a crucial rule in the regulation of gene transcription.
THE INVENTIONUW-Madison researchers have developed compounds and methods for specifically labeling the substrates of SAM-dependent methyltransferases. The methods use SAM analogs that have been modified at the C5` position so the analog is transferred by the methyltransferase to a methylation site in a substrate, such as a peptide or nucleic acid. Once anchored to the substrate, these cofactor analogs allow for the addition of a detectable and/or isolable label. The label may contain various moieties that aid in determining the methylation state of the substrate. The SAM analogs can also be used with nucleic acid methyltransferases to allow for the rapid identification of specific DNA or RNA residues that are typically methylated.
  • Determining the methylation state of a gene or gene promoter, such as those involved in imprinting and transcription regulation
  • May be used therapeutically to block DNA methylation or protein recognition of methylated DNA
  • Allows labeling of known or unknown methylation sites on DNA or proteins
  • Enables monitoring of methyltransferase activity without radioactivity
  • Provides a new approach to cancer treatment
  • May lead to greater understanding of biological methylation
  • Easily synthesized
  • Stable for long periods
  • Amenable to labeling with purification and/or reporter moieties
Contact Information
For current licensing status, please contact Rafael Diaz at or 608-960-9847.
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