V-shaped scaffold: A new architectural motif identified in an A center dot(G center dot G center dot G center dot G) pentad-containing dimeric DNA quadruplex involving stacked G(anti)center dot G(anti)center dot G(anti)center dot G(syn) tetrads

We report the results of an NMR study of unlabeled and uniformly C-13,N-15- labeled d(G(3)AG(2)T(3)G(3)AT) in 100 mM NaCl, conditions under which it fo rms a dimeric quadruplex containing several new topological features. The D NA oligomer chain in each symmetry-related monomer subunit undergoes three sharp turns to form a compact domain, with all the purine bases involved in pairing alignments. The first turn is of the double chain reversal type, t he second is of the edgewise type, and the third represents a new alignment , the V-shaped type. Each monomer of the dimeric quadruplex contains two st acked G(anti).G(anti).G(anti).G(syn) tetrads, one of which forms a newly id entified A.(G.G.G.G) pentad, through sheared G. mismatch formation. There i s a break in one of the four G. columns that link adjacent G.G.G.G tetrads within each monomer. This architectural interruption is compensated by a ne w topological feature of quadruplex architecture, the V-shaped scaffold. Th e missing G.G column results in an opening that could facilitate insertion of planar ligands into the quadruplex. The dimeric interface contains stack ed A.(G.G.G.G) pentads, with each pentad containing four bases from one mon omer and a syn G1 from the partner monomer. Several potential ligand-bindin g pockets, positioned towards either end of the folded architecture, were i dentifiable in a surface view of the solution structure of the dimeric d(G( 3)AG(2)T(3)G(3)AT) quadruplex. (C) 2001 Academic Press.