Syntrix Reports Discovery of Stem-Chelate-Loop Probe Exhibiting Reversible Metal-Dependent Destabilization and Stabilization of Binding to Unmodified DNA

Congratulations to Syntrix scientists on their latest publication, which appeared in the journal Bioconjugate Chemistry. Abstract: Herein, we report the discovery of a novel DNA probe with a stem-chelate-loop structure, wherein the stability of the probe-target duplex can be modulated lower or higher using a narrow concentration range of dilute transition metal ions (0.1-10 μM). Oligonucleotide probes containing two terpyridine (TPY) ligands separated by 15 bases of single-stranded DNA, with or without a flanking 5 base self-complementary DNA stem, were tested in thermal transition studies with linear target DNA and varying amounts of ZnCl(2). Without the stem, addition of Zn(2+) resulted only in reversible destabilization of the probe-target duplex, consistent with assembly (up to 1 equiv Zn(2+)) and disassembly (excess Zn(2+)) of the intramolecular Zn(2+)-(TPY)(2) chelate. Surprisingly, probes including both the intramolecular chelate and the stem gave a probe-target duplex that was reversibly destabilized and stabilized upon addition of Zn(2+) by ±5-7 °C, a phenomenon consistent with assembly and then disassembly of the entire stem-Zn(2+)-(TPY)(2) motif, including the DNA stem. Stemchelate-loop probes containing dipicolylamine (DPA) ligands exhibited no metal-dependent stabilization or destabilization. The stem-Zn(2+)-(TPY)(2) motif is readily introduced with automated synthesis, and may have broad utility in applications where it is desirable to have both upward and downward, reversible metal-dependent control over probe-target stability involving an unmodified DNA target

Link to paper.