Lindsay R. Comstock

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O-acetyl-ADP-ribose (OAADPr), produced by the Sir2-catalyzed NAD(+)-dependent histone/protein deacetylase reaction, regulates diverse biological processes. Interconversion between two OAADPr isomers with acetyl attached to the C-2″ and C-3″ hydroxyl of ADP-ribose (ADPr) is rapid. We reported earlier that ADP-ribosylhydrolase 3 (ARH3), one of three ARH(More)
Aziridine-based cofactor mimics have been synthesized and are shown to undergo methyltransferase-dependent DNA alkylation. Notably, each cofactor mimic possesses an azide functionality, to which can be attached an assortment of unnatural groups following methyltransferase-dependent DNA delivery. DNA duplexes modified with these cofactor mimics are capable(More)
We demonstrate here that MTase-modified DNA can undergo the Staudinger ligation with triarylphosphines derivatized with phenanthroline. Presentation of these duplexes with Cu(II) and 3-mercaptopropionic acid leads to strand scission proximal to the MTase recognition site. By virtue of their ability to use a synthetic azide-bearing cofactor, M.TaqI and(More)
Azide and alkyne-functionalized N-mustard analogues of S-adenosyl-L-methionine have been synthesized and were demonstrated to undergo efficient methyltransferase-dependent DNA alkylation by M.TaqI and M.HhaI. Subsequent labeling of the DNA with a fluorophore was carried out using copper-catalyzed azide-alkyne cycloaddition chemistry and was visualized by(More)
[reaction: see text] o-Carboalkoxy triarylphosphines are shown to react with aryl azides to provide Staudinger ligation products bearing O-alkyl imidate linkages. This is in contrast to alkyl azides whose ligation to o-carboalkoxy triarylphosphines has been reported to yield amide-linked materials. This extension of the Staudinger ligation for coupling of(More)
8-Azido-5'-aziridino-5'-deoxyadenosine (6), a novel cofactor mimic, was synthesized in nine steps from commercially available 2',3'-isopropylideneadenosine in approximately 4% overall yield. Crucial to this success was a very unorthodox phthalimide cleavage procedure, C8 azidation prior to aziridination and late stage alkylation of the 5' amino group with(More)
The synthesis of an azide-bearing N-mustard S-adenosyl-L-methionine (SAM) analogue, 8-azido-5'-(diaminobutyric acid)-N-iodoethyl-5'-deoxyadenosine, has been accomplished in 10 steps from commercially available 2',3'-isopropylidene adenosine. Critical to this success was executing C8 azidation prior to derivatizing the 5'-position of the ribose sugar and the(More)
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