Synthesis and characterization of a tetranucleotide analogue containing alternating phosphonate-amide backbone linkages.
Described herein is the synthesis and characterization of a tetranucleotide, 5'-dC-phosphonate-T-amide-T-ophosphonate-dC (III), in which the C-T and T-C steps contain a phosphonate backbone bond and T-T is a peptide nucleic acid dimer unit (neutral backbone). The 5'- and 3'-OH groups of the tetramer can be further derivatized and, thus, the compound is a potential building block for longer oligonucleotides which will contain alternating backbone modifications at designated positions. The synthesis involved first the preparation of two hybrid peptide-deoxyribose dinucleotides, CT-CO (I) and N-CT (II) (C and T are nucleobases; CO and N are carboxylic and amino terminal, respectively); each is linked through a phosphonate linkage. A condensation reaction between the two dimers, followed by deprotection, resulted in the formation of a peptide linkage to give the desired tetramer III. The reaction conditions used are mild to afford products in moderate to excellent yields. The DNA-PNA-DNA tetramer, d(CTTC), is a substrate for T4 kinase but fails to give a ligation product, even though NMR shows weak interactions between the tetramer III with its complementary sequence, d(GAAG).
Yu
P
P
Department of Chemistry University of Houston, TX 77204-5641, USA.
Wang
W
W
Zhang
H
H
Yang
X
X
Liang
T C
TC
Gao
X
X
D000577:Amides / Q000737:chemistry*; D011088:DNA Ligases; D019281:Dimerization; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009711:Nucleotides / Q000138:chemical synthesis*; D063065:Organophosphonates; D010766:Phosphorylation; D013698:Templates, Genetic
D000577:Amides; D009711:Nucleotides; D063065:Organophosphonates; D011088:DNA Ligases