Sequence dependence of Pd(II)-mediated base pairing by palladacyclic nucleobase surrogates

Abstract

<p>A <em>C</em>-nucleoside derivative of <a href="https://www.sciencedirect.com/topics/chemistry/phenylpyridine" title="Learn more about phenylpyridine from ScienceDirect's AI-generated Topic Pages">phenylpyridine</a> or the respective palladacycle was incorporated at either 3′- or 5′-terminus of a short oligodeoxynucleotide. Hybridization properties of these modified oligonucleotides were studied in a fluorescence-based competition assay in addition to conventional <a href="https://www.sciencedirect.com/topics/chemistry/uv-melting" title="Learn more about UV melting from ScienceDirect's AI-generated Topic Pages">UV melting</a> temperature analysis and compared with those of a previously prepared analogue featuring the modified nucleoside in the middle of the sequence. With the unpalladated phenylpyridine oligonucleotides, UV melting temperature qualitatively correlated with the ability to displace a strand from a double helix in the competition assay, decreasing in the order 5′ > 3′ > middle. Corresponding results on the palladacyclic oligonucleotides were more difficult to interpret but both UV melting and competition experiments revealed a decrease in the duplex stability upon palladation in most cases. On the other hand, dependence of the UV melting temperature on the identity of the canonical <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/nucleobase" title="Learn more about nucleobase from ScienceDirect's AI-generated Topic Pages">nucleobase</a> opposite to the modified nucleobase analogue was much more pronounced with the palladacyclic duplexes than with their unpalladated counterparts. Furthermore, UV melting profiles of the palladacyclic duplexes featured an additional transition at a temperature exceeding the melting temperature of the unmodified part of the duplex. Taken together, these results lend support to the idea of<br></p><div><div><p>Pd(II)-mediated base pairs that are highly stable but incompatible with the geometry of a double helix.</p></div></div><div><h2>Graphical abstract</h2><div><p>Hybridization properties of oligonucleotides incorporating a phenylpyridine C-nucleoside or its palladacyclic derivative were studied by a fluorescence-based competition assay in addition to conventional melting temperature measurements. Position of the modification had a major impact on duplex stability even when the canonical base opposite to the modified base remained unchanged.</p><p><br></p><p>.</p><p><img src="https://ars.els-cdn.com/content/image/1-s2.0-S0162013421001537-ga1.jpg" alt="Unlabelled Image"></p></div></div>