Effects of lupus‐inducing drugs on the B to Z transition of synthetic DNA

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Abstract
Five drugs associated with systemic lupus erythematosus were studied for their effect on the salt‐induced right‐handed (B) to left‐handed (Z) transition of poly(dG‐me5dC) · poly(dG‐me5dC). Using circular dichroism spectroscopy, procainamide and hydralazine were found to reduce the midpoint of B to Z transition from 0.8M NaCl to 0.5M NaCl and to increase the rate of this transition at 1M NaCl. Isoniazid and D‐penicillamine had less effect on the midpoint of transition and practically no effect on the kinetics. N‐acetyl procainamide (a structurally related control for procainamide) and L‐canavanine had no effect. Procainamide caused slight reduction in the helix‐coil transition (melting) temperature of calf thymus DNA. At a concentration of 1:1 (DNA phosphate: drug ratio), procainamide and hydralazine also caused the aggregation of calf thymus DNA. Since altered DNA conformations, such as Z‐DNA, are more immunogenic, these results suggest that the induction or stabilization of Z‐DNA by these drugs might be important in the pathogenesis of at least some cases of systemic lupus erythematosus.

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