Comparative study of berenil– and pentamidine–poly‐nucleotide complexes using UV/VIS and FTIR spectroscopy

Abstract

AbstractFourier‐transform infrared (FTIR) spectroscopy was applied to investigate the conformational aspects of the synthetic polynucleotides poly d(AT), poly(dA)·poly(dT), poly(dA)·poly(dT)*poly(dT) upon binding of berenil and pentamidine. Measurements were performed in D2O to elucidate the hydrogen bonding system in the adducts. It could be demonstrated that intermolecular H‐bonds were formed between the minor groove binders berenil or pentamidine and the polynucleotides. The drug‐nucleotide interaction is followed by weak conformational distortions of the alternating polynucleotide poly d(AT), whereas such an effect is negligible in the poly(dA)·poly(dT) complexes. The binding of berenil or pentamidine into the minor groove of the triple‐stranded polynucleotide poly(dA)·poly(dT)*poly(dT) did not induce a dissociation of the third strand [poly(dT)] from the helical major groove. However, thermal denaturation profiles obtained by UV/VIS spectroscopy revealed a destabilization of the triplex due to the ligation of the drug molecules. This effect was accompanied by a “decreased binding density” in the triple helix compared with the poly(dA)·poly(dT) duplex. In contrast, both double‐helical polynucleotides were stabilized by the minor groove binders. The influence of pentamidine on the helical stability was smaller. Utilizing the attenuated total reflection (ATR) technique, conformational transitions of the double helices induced by variation of the water content in the films were monitored. The addition of berenil was followed by a suppression of these transitions, whereas for pentamidine no similar effects were observed. © 1995 John Wiley & Sons, Inc.