(1S,2R/1R,2S)-cis-cyclopentyl PNAs (cpPNAs) as constrained PNA analogues: synthesis and evaluation of aeg-cpPNA chimera and stereopreferences in hybridization with DNA/RNA.
Conformationally constrained chiral PNA analogues were designed on the basis of stereospecific imposition of a 1,2-cis-cyclopentyl moiety on an aminoethyl segment of aegPNA. It is known that the cyclopentane ring is a relatively flexible system in which the characteristic puckering dictates the pseudoaxial/pseudoequatorial dispositions of substituents. Hence, favorable torsional adjustments are possible to attain the necessary hybridization-competent conformations when the moiety is imposed on the conventional PNA backbone. The synthesis of the enantiomerically pure 1,2-cis-cyclopentyl PNA monomers (10a and 10b) was achieved by stereoselective enzymatic hydrolysis of a key intermediate ester 2. The chiral (1S,2R/1R,2S)-aminocyclopentylglycyl thymine monomers were incorporated into PNA oligomers at defined positions and through the entire sequence. Hybridization studies with complementary DNA and RNA sequences using UV-Tm measurements indicate that aeg-cpPNA chimera form thermally more stable complexes than aegPNA with stereochemistry-dependent selective binding of cDNA/RNA. Differential gel shift retardation was observed on hybridization of aeg-cpPNAs with complementary DNA.
Govindaraju
T
T
Division of Organic Chemistry (Synthesis), National Chemical Laboratory, Pune, 411 008, India.
Kumar
Vaijayanti A
VA
Ganesh
Krishna N
KN
D001483:Base Sequence; D004247:DNA / Q000737:chemistry*; D015394:Molecular Structure; D009693:Nucleic Acid Hybridization; D020135:Peptide Nucleic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D012313:RNA / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
D020135:Peptide Nucleic Acids; D012313:RNA; D004247:DNA