Book of Abstracts: Albany 2005
Guanine Quadruplex Invasion by Complementary and Homologous PNA Probes
Peptide nucleic acid (PNA) oligomers consist of purine and pyrimidine nucleobases attached to a nonionic polyamide backbone. PNA probes hybridize with high affinity to complementary DNA and RNA sequences, even when the target sequence is part of a stable secondary or tertiary structure. This lecture will present recent results in using homologous PNA probes to target DNA and RNA guanine quadruplex structures, which are the focus of much recent attention as regulatory elements that control transcription and translation. Rather than forming Watson-Crick base pairs, homologous PNA probes form hybrid guanine tetrads consisting of two DNA or RNA guanines and two PNA guanines. Stacking of these tetrads leads to stable hybrid quadruplex structures. Results from both RNA and DNA quadruplex targets will be presented. The RNA target consists of quadruplex and duplex secondary structure elements and was derived from an in vitro selection experiment to obtain aptamers for the Fragile X mental retardation protein. The DNA target is based on a suppressor element found upstream of the main promoter for transcription of the c-MYC oncogene. These results extend the DNA and RNA sequence recognition capabilities of PNA probes to allow targeting of G quadruplexes using either complementary or homologous PNAs.
Bruce A. Armitage
Department of Chemistry