ISSN:
1434-193X
Keywords:
DNA recognition
;
Helical structures
;
Induced chirality
;
Peptide nucleic acid
;
Thermal stability
;
Chemistry
;
General Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
-Peptide Nucleic Acids (PNAs) are DNA mimics in which the deoxyribose phosphate backbone has been replaced by a pseudo-peptide skeleton composed of N-(2-aminoethyl)glycine units; they bind to complementary DNA strands with high affinity and selectivity. In order to study the effect of stereogenic centers within the backbone on PNA preorganization and DNA binding properties, chiral PNA decamers were synthesized which contained thymine monomers derived from L-Leu and D- or L-Lys inserted either at C-terminus and/or in the middle of an achiral PNA strand. PNAs containing three chiral thymine monomers derived from L-Leu, D- or L-Lys, L-Asp, or D-Glu were also synthesized. CD spectral analyses showed that a charged chiral monomer inserted in the middle of the strand is able to induce a strong preference in the helix handedness of a PNA-PNA duplex. The effect is increased by the presence of three chiral charged monomers. The L-Lys- and L-Asp-PNAs induced a preference for the left-handed and the D-Lys and D-Glu-PNAs for the right-handed conformation. As expected, the PNA-DNA duplexes are dominated by the DNA strand and thus are right-handed with both D- and L-PNAs. However, the D-PNAs, being inherently right-handed, lead to more stable PNA-DNA duplexes than the L-PNAs. The lysine-based PNAs form more stable complexes with the DNA at low ionic strength, due to the electrostatic interactions between the charged lysine side chain and DNA.
Additional Material:
10 Ill.
Type of Medium:
Electronic Resource
