Synthesis and Photochemical Behavior of Peptide Nucleic Acid Dimers and Analogues Containing 4-Thiothymine:  Unprecedented (5−4) Photoadduct Reversion

• Published in: Journal of the American Chemical Society Vol. 120; no. 6; pp. 1157 - 1166
• Main Authors: Clivio, Pascale, Guillaume, Dominique, Adeline, Marie-Thérèse, Hamon, Jeanine, Riche, Claude, Fourrey, Jean-Louis
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 18.02.1998; Amer Chemical Soc
• Subjects: 4-thiothymine; Chemistry; Chemistry, Multidisciplinary; N@u3-methyl-4-thiothymine; Peptide nucleic acids; Physical Sciences; Science & Technology; PHOTOPRODUCTS; MONOMERS; PNA-DNA; THYMINE; (6-4)-PHOTOPRODUCT DNA PHOTOLYASE; ULTRAVIOLET LIGHT; TRANSFER-RNA; 4-THIOURIDINE; OLIGOMERIZATION; UV IRRADIATION
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja971983b

PNA dimers 1−5, containing either 4-thiothymine or N 3-methyl-4-thiothymine, were prepared, and the crystal structure of compound 3 was established. With regard to their photochemistry, none of these PNA analogues were able to fully mimic the photochemical behavior observed in the dinucleotide series. Whereas 1 and 2 displayed a sequence dependent photochemistry to give mainly 4-(α-thyminyl) adducts, their rearranged isomers 3 and 4 yielded mostly (5−4) photoadducts. Photoproducts originating from 3 and 4 were shown to undergo spontaneous reversal to their dithyminyl parent derivatives under acid conditions. Moreover, as a result of this photochemical study, it can be suggested that in solution, even at the dimer stage, PNAs adopt a conformation reminiscent of A-type DNA.