Synthesis of pyrrolidinone PNA: a novel conformationally restricted PNA analogue.
To preorganize PNA for duplex formation, a new cyclic pyrrolidinone PNA analogue has been designed. In this analogue the aminoethylglycine backbone and the methylenecarbonyl linker are connected, introducing two chiral centers compared to PNA. The four stereoisomers of the adenine analogue were synthesized, and the hybridization properties of PNA decamers containing one analogue were measured against complementary DNA, RNA, and PNA strands. The (3S,5R) isomer was shown to have the highest affinity toward RNA, and to recognize RNA and PNA better than DNA. The (3S,5R) isomer was used to prepare a fully modified decamer which bound to rU10 with only a small decrease in Tm (delta Tm/mod = 1 degree C) relative to aminoethylglycine PNA.
Püschl
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A
Center for Biomolecular Recognition, Department for Biochemistry and Genetics, Biochemistry Laboratory B, Panum Institute, Blegdamsvej 3C, DK-2200, Copenhagen, Denmark.
Boesen
T
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Zuccarello
G
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Dahl
O
O
Pitsch
S
S
Nielsen
P E
PE
D009682:Magnetic Resonance Spectroscopy; D009690:Nucleic Acid Conformation; D020135:Peptide Nucleic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D011760:Pyrrolidinones / Q000737:chemistry*; D016339:Spectrometry, Mass, Fast Atom Bombardment
D020135:Peptide Nucleic Acids; D011760:Pyrrolidinones