A Universal, Photocleavable DNA Base:  Nitropiperonyl 2‘-Deoxyriboside

Abstract

A universal, photochemically cleavable DNA base analogue would add desirable versatility to a number of methods in molecular biology. A novel C-nucleoside, nitropiperonyl deoxyriboside (NPdR, P), has been investigated for this purpose. NPdR can be converted to its 5'-DMTr-3'-CE-phosphoramidite and was incorporated into pentacosanucleotides by conventional synthesis techniques. The destabilizing effect on hybrid formation with a complementary strand when this P base opposes A, T, and G was found to be 3-5 kcal/mol, but 9 kcal/mol when it opposes C. Brief irradiation (lambda > 360 nm, 20 min) of DNA containing the P base and piperidine treatment causes strand cleavage giving the 3'- and 5'-phosphates. Two significant recent interests, universal/non-hydrogen-bonding base analogues and photochemical backbone cleavage, have thus been combined in a single molecule that serves as a light-based DNA scissors.

The Effect of Hydrogen Bonding on Allylic Alkylation and Isomerization Reactions in Ionic Liquids

“…194 A similar system is available for RNA abasic site generation 195. While some systems require (partly) additional treatment after photoactivation,196–198 others do not.…”

Universal Base Analogues and their Applications to Biotechnology

“…Moreover, 39 was only destabilizing by an average of 7 C compared to the natural base pair. Also, 39 could be used as a light-based DNA scissors as it can be readily cleaved by irradiation (l > 360 nm, 20 min), followed by piperidine treatment [78]. In this case, photolysis of DNA containing 39 results in chain cleavage leading to excision of the nucleoside analogue generating an oligonucleotide-3 0 -phosphate.…”

Biologisch aktive Moleküle mit “Lichtschalter”

“…194 Zur Bildung einer abasischen Stelle in der RNA ist ein ähnliches System vorhanden 195. Einige Systeme erfordern eine zusätzliche Behandlung nach der Photoaktivierung 196–198…”