Figure 11

Proposed mechanism for the increased binding affinity of duplexes with Group II base bulges . The Group I base bulge (A), originating from the insertion of the unpaired base 'A', creates a 1-nt frameshift between the complementary probe and target sections, and thus acts like a barrier delaying the formation of a stable duplex. The bulged 'A' needs to adopt a favorable (e.g. looped out) conformation, so that the frameshift is compensated and the zipping of complementary base pairs can continue. Unlike the Group I base bulge in (A) the Group II base bulge in (B), originating from the insertion of the surplus base 'T' next to another 'T', is degenerate. Since there is an increased probability that any of the two degenerate bases adopts a favorable conformation, while simultaneously the subsequent base is forming a base pair with the corresponding base in the opposite strand (so that the frameshift is overcome), the formation of a stable duplex is accelerated.