%0 Journal Article
%T Effect of Steric Constraint at the ¦Ã-Backbone Position on the Conformations and Hybridization Properties of PNAs
%A Matthew J. Crawford
%A Srinivas Rapireddy
%A Raman Bahal
%A Iulia Sacui
%A Danith H. Ly
%J Journal of Nucleic Acids
%D 2011
%I Hindawi Publishing Corporation
%R 10.4061/2011/652702
%X Conformationally preorganized peptide nucleic acids (PNAs) have been synthesized through backbone modifications at the ¦Ã-position, where R = alanine, valine, isoleucine, and phenylalanine side chains. The effects of these side-chains on the conformations and hybridization properties of PNAs were determined using a combination of CD and UV-Vis spectroscopic techniques. Our results show that the ¦Ã-position can accommodate varying degrees of sterically hindered side-chains, reaffirming the bimodal function of PNAs as the true hybrids of ¡°peptides¡± and ¡°nucleic acids.¡± 1. Introduction Oligonucleotides are becoming increasingly important in the postgenomic era, as molecular tools for basic research as well as potential therapeutic and diagnostic reagents for the treatment and detection of genetic diseases [1¨C4]. However, for many of the in vivo applications, it is not sufficed just to be able to design oligonucleotide reagents that can recognize and bind sequence specifically to DNA or RNA. These reagents would also need to be able to get into cells and withstand enzymatic degradation by nucleases in the cellular milieu. To date, diverse classes of oligonucleotide analogues have been developed, but none possesses all the characteristic features [5¨C8]. It is, therefore, important to be able to modify the structures and/or chemical functionalities of these reagents further, with ease and flexibility, so that many of these desired features could be augmented and/or improved upon [9, 10] and undesired attributes, such as nonspecific binding and toxicity, could be further minimized [11, 12]. A particular class of oligonucleotide analogue endowed with such synthetic flexibility is peptide nucleic acids (PNAs) [13]. PNAs are nucleic acid mimics, comprised of N-(2-aminoethyl) glycine backbone and DNA/RNA nucleobases that are connected through a flexible carboxymethylene linker. Despite the structural departure from the natural biopolymers, PNAs maintain the ability to hybridize to complementary DNA and RNA strands through Watson-Crick base-pairing, just as their natural counterparts, but with higher affinity and sequence selectivity. The improvement in binding affinity has been attributed in part to the lack of electrostatic repulsion in the backbones [14], while the enhancement in sequence selectivity has been attributed in part to the increased backbone rigidity upon hybridization as the result of solvation [15, 16]. Unlike DNA or RNA, which are prone to nucleolytic degradation, PNAs are resistant to both proteases and nucleases. These properties, together with
%U http://www.hindawi.com/journals/jna/2011/652702/