Synthesis and Molecular Modelling of Double-Functionalised Nucleosides with Aromatic Moieties in the 5′-(S)-Position and Minor Groove Interactions in DNA Zipper Structures

• Published in: Chemistry : a European journal Vol. 16; no. 43; pp. 12904 - 12919
• Main Authors: Shaikh, Khalil Isak, Madsen, Charlotte Stahl, Nielsen, Lise Junker, Jørgensen, Anna Søndergaard, Nielsen, Henrik, Petersen, Michael, Nielsen, Poul
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 15.11.2010; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Subjects: Aromatics; Base pairs; Chemistry; Chemistry, Multidisciplinary; Click Chemistry; Deoxyribonucleic acid; DNA; DNA - chemistry; Grooves; Melting; Modelling; Models, Molecular; Molecular modelling; molecular recognition; Molecular structure; nanobiotechnology; Nanotechnology; Nucleic Acid Conformation; Nucleosides; Nucleosides - chemical synthesis; Nucleosides - chemistry; Phenyls; Physical Sciences; Science & Technology; Sequence Homology, Nucleic Acid; Spectroscopy; Stacking; stacking interactions; Thymine; Zippers; click chemistry; nanobiotechnology; stacking interactions; MAIN-GROUP ELEMENTS; TRANSITION-METALS; EPOXIDATION; ACID SECONDARY STRUCTURES; OLIGONUCLEOTIDES; CLICK CHEMISTRY APPROACH; CYCLOADDITION; AMBER; DNA; molecular recognition; MULTIPLE BONDS; DUPLEX
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.201001253

A series of six double‐functionalised nucleosides, in which aromatic moieties were inserted into the 5′‐(S)‐C‐position, were synthesised and incorporated into DNA duplexes. The aromatic moieties were thymine‐1‐yl, phenyl, 1,2,3‐triazol‐1‐yl, 1,2,3‐triazol‐4‐yl, 4‐(uracil‐5‐yl)‐1,2,3‐triazol‐1‐yl and 4‐phenyl‐1,2,3‐triazol‐1‐yl. The DNA duplexes were studied with UV melting curves, CD spectroscopy and molecular modelling. The results showed that the aromatic moieties in some cases interact in the minor groove forming DNA zipper structures. The strongest specific interaction was found between two thymines or between a thymine and a phenyl group in a crossed (−3)‐zipper motif (i.e., with two base pairs interspacing the modifications). Modelling revealed that the interaction is aromatic stacking across the minor groove. Also, the extended uracil‐triazole moiety demonstrated zipper contacts in the minor groove as well as binding to the floor of the groove. Communication in the minor groove: A series of aromatic moieties were inserted in the minor groove of DNA through 5′‐(S)‐C‐substituted nucleosides. A strong and specific interaction was found between a thymine and a phenyl group in a crossed (−3)‐zipper motif. Modelling revealed that the interaction is due to aromatic stacking across the minor groove (see figure).