INTER-STRAND C-H-CENTER-DOT-CENTER-DOT-CENTER-DOT-O HYDROGEN-BONDS STABILIZING 4-STRANDED INTERCALATED MOLECULES - STEREOELECTRONIC EFFECTSOF 04' IN CYTOSINE-RICH DNA

DNA fragments with stretches of cytosine residues can fold into four-s tranded structures in which two parallel duplexes, held together by he miprotonated cytosine . cytosine(+) (C . C+) base pairs, intercalate i nto each other with opposite polarity. The structural details of this intercalated DNA quadruplex have been assessed by solution NMR and sin gle crystal x-ray diffraction studies of cytosine-rich sequences, incl uding those present in metazoan telomeres. A conserved feature of thes e structures is the absence of stabilizing stacking interactions betwe en the aromatic ring systems of adjacent C . C+ base pairs from interc alated duplexes. Effective stacking involves only the exocyclic keto g roups and amino groups of the cytidine bases, The apparent absence of stability provided by stacking interactions between the bases in this intercalated DNA has prompted us to examine the available structures i n detail, in particular with regard to unusual features that could com pensate for the lack of base stacking. In addition to base-on-deoxyrib ose stacking and intra-cytidine C-H ... O hydrogen bonds, this analysi s reveals the presence of a hitherto unobserved, systematic intermolec ular C-H ... O hydrogen bonding network between the deoxyribose sugar moieties of antiparallel backbones in the four-stranded molecule.