688318-57-2Relevant academic research and scientific papers
The α-Helical Peptide Nucleic Acid Concept: Merger of Peptide Secondary Structure and Codified Nucleic Acid Recognition
Huang, Yumei,Dey, Subhakar,Zhang, Xiao,Soennichsen, Frank,Garner, Philip
, p. 4626 - 4640 (2004)
A novel platform for nucleic acid recognition that integrates the α-helix secondary structure of peptides with the codified base-pairing capability of nucleic acids is reported. The resulting α-helical peptide nucleic acids (αPNAs) are composed of a repeating tetrapeptidyl unit, aa1-aa2-aa3-SerB, where aa 1 through aa3 represent generic ancillary amino acids and B = nucleobases linked to Ser via a methylene bridge. Effective syntheses of constituent Fmoc-protected nucleoamino acids (Fmoc-SerB-OH, where B = thymine, cytosine, and uracil) are described along with a protocol for the solid-phase synthesis of 21mer αPNAs containing five such nucleobases. By varying the ancillary amino acids, two distinct classes of αPNAs were constructed, having a net charge of -1 or +6, respectively, at physiological pH. The modular nature of the αPNA platform was illustrated by the synthesis of symmetrical disulfide-bridged αPNA dimers containing 10 nucleobases. Hybridization of these αPNAs with ssDNA has been examined by thermal denaturation, gel electrophoresis, and circular dichroism (CD) and the data indicated that αPNA binds to ssDNA in a cooperative manner with high affinity and sequence specificity. In general, b2 αPNAs bind faster and more strongly with ssDNA than do the corresponding b1 αPNAs. Parallel αPNA-DNA complexes are more stable than their antiparallel counterparts. CD studies also revealed that the hybridization event involves the folding of both species into their helical conformations. Finally, NMR experiments provided conclusive evidence of Watson-Crick base pairing in αPNA-ssDNA hybrids.
