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Design of an Intercalating Linker Leading to the First Efficiently 5′,5′‐Linked Alternate‐Strand Hoogsteen Triplex with High Stability and Specificity
Author(s) -
Jessen Carsten H.,
Pedersen Erik B.
Publication year - 2004
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200490220
Subject(s) - chemistry , linker , stacking , sonogashira coupling , intercalation (chemistry) , conjugated system , stereochemistry , molecule , iodobenzene , crystallography , combinatorial chemistry , organic chemistry , polymer , palladium , computer science , catalysis , operating system
This is the first report describing the design, synthesis, and incorporation of an intercalating linker leading to an efficiently 5′,5′‐linked alternate strand Hoogsteen triplex. Using molecular modeling, the 5′,5′ problem was solved in a rather simple way. The two relatively distant 5′‐ends have been connected with a molecule that provides rigidity to the structure, while being flexible enough to allow stacking upon all four strands. The synthesis of the core of the designed molecule was conducted by Sonogashira coupling of an appropriately substituted iodobenzene with 1,3‐diethynylbenzene to give a conjugated system with three benzene rings interconnected with triple bonds. For the alternate‐strand triplex obtained with the intercalating linker, the stability obtained is higher than that of the corresponding homotriplex of equivalent total length and with the same nucleotides. This is deduced from a 5° higher melting temperature of the alternating triplex. The sensitivity towards mismatches in the alternate‐strand triplex is in the same range (Δ T m =−13° to −19°) as those observed for homotriplexes.