EFFECTS OF NATURAL AND SYNTHETIC POLYAMINES ON THE CONFORMATION OF ANOLIGODEOXYRIBONUCLEOTIDE WITH THE ESTROGEN RESPONSE ELEMENT

We studied the effects of natural and synthetic polyamines on the conf ormation of an oligodeoxyribonucleotide (ODN1) harboring the estrogen response element (ERE) by circular dichroism (CD) spectroscopy and pol yacrylamide gel electrophoresis. Putrescine and spermidine had no mark ed effect on the CD spectrum of ODN1. In contrast, spermine provoked a nd stabilized two characteristic changes in the CD spectrum. The first change was indicated by an increase in the intensity of the CD band a t 280 nm at 0.5 mM spermine in Tris-HCI buffer containing 50 mM NaCl. This change appears to be related to changes in base tilt and conforma tional alterations similar to A-DNA. At 1-2 mM spermine, the CD spectr um was characterized by a loss of positive bands at 220 and 270 nm. Th is change might have contributions from polyamine-induced condensation /aggregation of DNA. Spectral measurements were also conducted in Tris -HCI buffer containing 150 mM NaCl to minimize contributions from cond ensation and aggregation of ODN1. Under these conditions, CD spectral changes were retained by (ODN1), although the magnitude of the change was diminished. In contrast, a control oligdeoxyribonucleotide (ODN2) having similar base composition did not show any significant change in the CD spectrum in the presence of 150 mM NaCl and 2 mM spermine. The changes in the CD spectrum of ODN1 were highly sensitive to polyamine structure, as evidenced by experiments using spermine analogs with al tered number of -CH2- groups separating the amino and imino groups. El ectrophoretic mobility shift analysis further showed ODN1 stabilizatio n by spermine and its analogs. These data demonstrate the ability of a n ODN containing ERE to undergo conformational transitions in the pres ence of polyamines and suggest a possible mechanism for polyamine-medi ated alterations in the interaction of estrogen receptor with ERE.