A Synthetic DNA with Unusual Base‐Pairing

The alternating polydeoxynucleotide poly[d(A‐s 4 T) · d(A‐s 4 T)] with 4‐thiothymidine substituting for thymidine shows anomalous spectral and hydrodynamic properties which are inconsistent with a Watson‐Crick structure but agree with a model of a left‐handed double helix built up from Haschemeyer‐Sobell (reversed Hoogsteen) base‐pairs instead. Optical‐rotatory‐dispersion and circular‐dichroism spectra exhibit a strong negative Cotton effect centered near 400 nm that is assigned to a n →π* transition of the thioamide chromophor and that is at least unexpected if the sulfur atom participates in the hydrogen bridge. From the inversion of the Cotton effects between 370 and 400 nm with respect to the monomer or randomcoil state it is inferred that 4‐thiothymidine attains the unusual syn conformation in the ordered polymer. At pH below 4.5 the polymer is protonated at N‐1 of the deoxyadenosine residues and changes into a different helical conformation. As the inflection point of the proton‐induced transition falls close to the basic pK of deoxyadenosine monophosphate, also N‐1 (A) is probably not involved in hydrogen bonding. Therefore, only N‐7 (A) and 0‐2 (s 4 T) remain as proton acceptors for base‐pairing. The polymer undergoes cooperative temperature‐dependent transitions in concentrated solutions of 1:1 electrolytes. Two more helical conformations are characterized by ultraviolet, optical‐rotatory dispersion, and circular dichroism. In addition, changes in hydrodynamic parameters, e.g. sedimentation coefficient, buoyant density and partial specific‐volume are reported. A structural hysteresis is observed in a helix‐helix transition and is discussed in terms of metastable states indicated from a phase diagram.