Synthesis and evaluation of (1S,2R/1R,2S)-aminocyclohexylglycyl PNAs as conformationally preorganized PNA analogues for DNA/RNA recognition.
Conformationally constrained cis-aminocyclohexylglycyl PNAs have been designed on the basis of stereospecific imposition of 1,2-cis-cyclohexyl moieties on the aminoethyl segment of aminoethylglycyl PNA (aegPNA). The introduction of the cis-cyclohexyl ring may allow the restriction of the torsion angle beta in the ethylenediamine segment to 60-70 degrees that is prevalent in PNA(2):DNA and PNA:RNA complexes. The synthesis of the optically pure monomers (10a and 10b) is achieved by stereoselective enzymatic hydrolysis of an intermediate ester 2. The chiral PNA oligomers were synthesized with (1S,2R/1R,2S)-aminocyclohexylglycyl thymine monomers in the center and N-terminus of aegPNA. Differential gel shift retardation with one or more units of modified monomer units was observed as a result of hybridization of PNA sequences with complementary DNA sequences. Hybridization studies with complementary DNA and RNA sequences using UV-T(m) measurements indicate that PNA with (1S,2R)-cyclohexyl stereochemistry enhances selective binding with RNA over DNA as compared to control aegPNA and PNA with the other (1R,2S) isomer.
Govindaraju
T
T
Division of Organic Chemistry (Synthesis), National Chemical Laboratory, Pune 411008, India.
Kumar
Vaijayanti A
VA
Ganesh
Krishna N
KN
D000438:Alcohols / Q000737:chemistry; D001667:Binding, Competitive; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D018076:DNA, Complementary / Q000737:chemistry; D024202:Electrophoretic Mobility Shift Assay; D008049:Lipase; D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization; D020135:Peptide Nucleic Acids / Q000138:chemical synthesis*; D012313:RNA / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D013696:Temperature; D013941:Thymine / Q000031:analogs & derivatives
D000438:Alcohols; D018076:DNA, Complementary; D020135:Peptide Nucleic Acids; D012313:RNA; D004247:DNA; D008049:Lipase; D013941:Thymine