Sequence‐Dependent Duplex Stabilization upon Formation of a Metal‐Mediated Base Pair

Abstract

An artificial nucleoside surrogate with 1H-imidazo[4,5-f][1,10]phenanthroline (P) acting as an aglycone has been introduced into DNA oligonucleotide duplexes. This nucleoside surrogate can act as a bidentate ligand, and so is useful in the context of metal-mediated base pairs. Several duplexes involving a hetero base pair with an imidazole nucleoside have been investigated. The stability of DNA duplexes incorporating the respective Ag(I) -mediated base pairs strongly depends on the sequence context. Quantum mechanical/molecular mechanical (QM/MM) calculations have been performed in order to gain insight into the factors determining this sequence dependence. The results indicated that, in addition to the stabilizing effect that results from the formation of coordinative bonds, destabilizing effects may occur when the artificial base pair does not fit optimally into the surrounding B-DNA duplex.

A metal-mediated base pair that discriminates between the canonical pyrimidine nucleobases

“…The sequence was chosen because it had previously been used for the characterization of metal-mediated base pairs formed from P :imidazole hetero mispairs, allowing an optimal comparison. 17 In the present study, cytosine ( C ) or thymine ( T ) were used as the complementary nucleoside denoted X in Chart 2. Information on the stability of the unnatural base pairs was derived from the melting temperatures T m of the corresponding duplexes, determined by using temperature-dependent UV spectroscopy.…”

“…16,17 The synthesis of 1 is reported in the ESI †. 6-Carboxyfluorescein (6-FAM CPG), 5′-dabcyl phosphoramidite and the phosphoramidites of the natural nucleosides were purchased from Glen Research.…”

“…Toward this end, the ligand 1 H -imidazo[4,5- f ][1,10]phenanthroline was used as artificial nucleobase. We could previously show that a nucleoside analogue P (Chart 1) bearing this nucleobase is capable of forming Ag + -mediated homo base pairs 16 as well as hetero base pairs 17 with an artificial imidazole nucleoside. In this study, we establish its use in the discrimination of the canonical nucleobases cytosine and thymine by developing a turn-on fluorescence sensor.…”

Artificial DNA Base Pairing Mediated by Diverse Metal Ions

“…91 The idea of metal-mediated base pairs has been applied to nucleic acids analogues and other DNA structures. As already mentioned, some metallo-base pairs have been successfully incorporated into glycol nucleic acid (GNA) 34 25 or triazole base pairs (TriAg I Tri). 104 For example, a self-complementary DNA strand d(5¤-TTA ATT TImIm ImAA ATT AA-3¤) folded into a hairpin structure in the absence of transition metal ions.…”

“…In one of the investigated DNA sequences, ¦T m M for the formation of an ImAg I Imp base pair amounts to +10°C, whereas only +1°C was found for the "inverse" ImpAg I Im base pair within the same sequence. 34 Structure calculations revealed that in the latter case, the metal-mediated base pair induced distortions in the neighboring canonical base pairs, so that the stabilizing effect due to the formation of coordinate bonds was consumed by the destabilizing effect due to the distorted backbone. Hence, this example shows that also the metal complex may impose its structure onto the nucleic acid duplex.…”