Synthesis and properties of PNA oligomers containing orotic acid derivatives.
We have investigated the incorporation of C6-derivatives of uracil into polypyrimidine peptide nucleic acid oligomers (PNA). Starting with orotic acid (uracil-6-carboxylic acid) we have prepared a PNA monomer containing the methyl orotate nucleobase which is compatible with Fmoc-based synthesis. Treatment of the resin-bound oligomers with hydroxide or amines cleanly converted the ester to an orotic acid or orotamide-containing PNA. Alternatively, the methyl orotate-containing PNA was liberated from the resin by standard acidolysis. PNA bearing a modified nucleobase was found to hybridize to both poly(rA) and poly(dA). Complexes with poly(rA) were more stable than those with poly(dA) but both were destabilized relative to an unmodified PNA. Modification of a terminal residue was tolerated better than modification of an internal position. The type of charge provided by the modification affected the complex stability. In the worst case, an internal modification was nearly as detrimental as a base mismatch.
Hudson
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Department of Chemistry, University of Western Ontario, London, Ontario N6A 5B7, Canada.
Wojciechowski
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D001482:Base Composition; D020137:Base Pair Mismatch; D008956:Models, Chemical; D008968:Molecular Conformation; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D009841:Oligonucleotides / Q000737:chemistry; D009963:Orotic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D020135:Peptide Nucleic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D011061:Poly A / Q000737:chemistry; D017434:Protein Structure, Tertiary; D055672:Static Electricity
D009838:Oligodeoxyribonucleotides; D009841:Oligonucleotides; D020135:Peptide Nucleic Acids; D011061:Poly A; C015465:poly(dA); D009963:Orotic Acid