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Article

Effect of PNA Backbone Modifications on Cyanine Dye Binding to PNA−DNA Duplexes Investigated by Optical Spectroscopy and Molecular Dynamics Simulations

Supporting Info

Isil Dilek,^† Marcela Madrid,^‡ Rojendra Singh,^† Christian P. Urrea,^† and Bruce A. Armitage*^†

Contribution from the Pittsburgh Supercomputing Center and Department of Chemistry, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, Pennsylvania 15213

J. Am. Chem. Soc., 2005, 127 (10), pp 3339–3345

DOI: 10.1021/ja045145a

Publication Date (Web): February 18, 2005

†

Department of Chemistry.

‡

Pittsburgh Supercomputing Center.

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

army@andrew.cmu.edu

Abstract

Optical spectroscopy and molecular dynamics simulations have been used to study the interaction between a cationic cyanine dye and peptide nucleic acid (PNA)−DNA duplexes. This recognition event is important because it leads to a visible color change, signaling successful hybridization of PNA with a complementary DNA strand. We previously proposed that the dye recognized the minor groove of the duplex, using it as a template for the assembly of a helical aggregate. Consistent with this, we now report that addition of isobutyl groups to the PNA backbone hinders aggregation of the dye when the substituents project into the minor groove but have a weaker effect if directed out of the groove. UV−Visible and circular dichroic spectroscopy were used to compare aggregation on the different PNA−DNA duplexes, while molecular dynamics simulations were used to confirm that the substituents block the minor groove to varying degrees, depending on the configuration of the starting amino acid. In addition to a simple steric blockage effect of the substituent, the simulations suggest that directing the isobutyl group into the minor groove causes the groove to narrow and the duplex to become more rigid, structural perturbations that are relevant to the growing interest in backbone-modified PNA for applications in the biological and materials sciences.

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