A Simple γ-Backbone Modification Preorganizes Peptide Nucleic Acid into a Helical Structure

• Published in: Journal of the American Chemical Society Vol. 128; no. 31; pp. 10258 - 10267
• Main Authors: Dragulescu-Andrasi, Anca, Rapireddy, Srinivas, Frezza, Brian M, Gayathri, Chakicherla, Gil, Roberto R, Ly, Danith H
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 09.08.2006; Amer Chemical Soc
• Subjects: Analytical, structural and metabolic biochemistry; Biological and medical sciences; Carbohydrates. Nucleosides and nucleotides; Chemistry; Chemistry, Multidisciplinary; Circular Dichroism; Dimerization; Dna, deoxyribonucleoproteins; Exact sciences and technology; Fundamental and applied biological sciences. Psychology; Models, Molecular; Nuclear Magnetic Resonance, Biomolecular; Nucleic Acid Conformation; Nucleic acids; Nucleosides, nucleotides and oligonucleotides; Organic chemistry; Peptide Nucleic Acids - chemistry; Physical Sciences; Preparations and properties; Science & Technology; Temperature; PNA ANALOGS; DNA-BINDING; MONOMERS; RECOGNITION; RNA; DYNAMICS; CHIRAL PNA; HYBRIDIZATION; THYMINE; OLIGONUCLEOTIDES; Nucleotide; Peptide nucleic acid; Helical structure; Antisense oligonucleotide
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja0625576

Peptide nucleic acid (PNA) is a synthetic analogue of DNA and RNA, developed more than a decade ago in which the naturally occurring sugar phosphate backbone has been replaced by the N-(2-aminoethyl) glycine units. Unlike DNA or RNA in the unhybridized state (single strand) which can adopt a helical structure through base-stacking, although highly flexible, PNA does not have a well-defined conformational folding in solution. Herein, we show that a simple backbone modification at the γ-position of the N-(2-aminoethyl) glycine unit can transform a randomly folded PNA into a helical structure. Spectroscopic studies showed that helical induction occurs in the C- to N-terminal direction and is sterically driven. This finding has important implication not only on the future design of nucleic acid mimics but also on the design of novel materials, where molecular organization and efficient electronic coupling are desired.