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Article

Thermodynamics and Kinetics of PNA−DNA Quadruplex-Forming Chimeras

Supporting Info

Luigi Petraccone,^† Bruno Pagano,^† Veronica Esposito,^‡ Antonio Randazzo,^‡ Gennaro Piccialli,^‡ Guido Barone,^§ Carlo A. Mattia,^† and Concetta Giancola*^§

Contribution from the Dipartimento di Scienze Farmaceutiche, Via Ponte Don Melillo, 84084, Fisciano (SA), Italy, Dipartimento di Chimica delle Sostanze Naturali, Via D. Montesano 49, Universit Federico II di Napoli, 80131, Naples, Italy, and Dipartimento di Chimica, Via Cintia, Universit Federico II di Napoli, 80126, Naples, Italy

J. Am. Chem. Soc., 2005, 127 (46), pp 16215–16223

DOI: 10.1021/ja0545923

Publication Date (Web): October 26, 2005

†

Dipartimento di Scienze Farmaceutiche, Via Ponte Don Melillo.

‡

Dipartimento di Chimica delle Sostanze Naturali, Università “Federico II” di Napoli.

Dipartimento di Chimica, Università “Federico II” di Napoli.

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

, giancola@unina.it

Abstract

PNA−DNA chimeras present the interesting properties of PNA, such as the high binding affinity to complementary single-strand (DNA or RNA), and the resistance to nuclease and protease degradation. At the same time, the limitations of an oligomer containing all PNA residues, such as low water solubility, self-aggregation, and low cellular uptake, are effectively overcome. Further, PNA−DNA chimeras possess interesting biological properties as antisense agents. We have explored the ability of PNA−DNA chimeric strands to assemble in quadruplex structures. The rate constant for association of the quadruplexes and their thermodynamic properties have been determined by CD spectroscopy and differential scanning calorimetry (DSC). Thermal denaturation experiments indicated higher thermal and thermodynamic stabilities for chimeric quadruplexes in comparison with the corresponding unmodified DNA quadruplex. Singular value decomposition analysis (SVD) suggests the presence of kinetically stable intermediate species in the quadruplex formation process. The experimental results have been discussed on the basis of molecular dynamic simulations. The ability of PNA−DNA chimeras to form stable quadruplex structures expands their potential utility as therapeutic agents.

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