Mimics of small ribozymes utilizing a supramolecular scaffold.

For elucidating the mechanism of the general acid/base catalysis of the hydrolysis of RNA phosphodiester bonds, a number of cleaving agents having two cyclen moieties tethered to a 1,3,5-triazine core have been prepared and their ability to bind and cleave uridylyl-3',5'-uridine (UpU) studied over a wide pH range. Around neutral pH, the cleaving agents form a highly stable ternary complex with UpU and Zn(II) through coordination of the uracil N3 and the cyclen nitrogen atoms to the Zn(II) ions. Under conditions where the triazine core exists in the deprotonated neutral form, hydrolysis of UpU, but not of adenylyl-3',5'-adenosine (ApA), is accelerated by approximately two orders of magnitude in the presence of the cleaving agents, suggesting general base rather than metal ion catalysis.

Synthesis of oligonucleotide glycoconjugates using sequential click and oximation ligations.

Oligodeoxyribonucleotide glycoconjugates bearing two trivalent glycoclusters have been synthesized by two alternative methods based on solid-supported oximation of aminooxy functionalized oligonucleotides with glycoclusters constructed by click chemistry. In more detail, the trivalent glycoclusters (5 and 6) bearing three sugar pendants were first assembled by treating a 4-[tri-O-propargylpentaerythrityloxy]benzaldehyde scaffold with methyl 6-azido-6-deoxyglycopyranoside under the click reaction conditions. Two phosphoramidite reagents containing a phthaloyl protected aminooxy function, viz.