Spectroscopic studies on double-stranded poly d[(G-C)(G-C)] in B and Z form after covalent modification with the anti diastereomer of trans-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene.
Spectroscopic studies on double-stranded poly d[(G-C)(G-C)] in B and Z form after covalent modification with the anti diastereomer of trans-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene.
复制标题
用反式-7,8-二羟基-9,10-环氧-7,8,9,10的反非对映异构体共价修饰后B和Z形式的双链聚d[(G-C)(G-C)]的光谱研究
作者：
I. Zegar;P. Lycksell;A. Gräslund;M. Eriksson;B. Nordén;B. Jernström
Poly d[(G-C)(G-C)] in B or Z conformation has been incubated with the anti-diastereomer of trans-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE). Enzymatic hydrolysis, circular dichroism (CD) and light absorption were used to study the binding specificity of anti-BPDE to the right- and left-handed forms of poly d[(G-C)(G-C)]. The effect of anti-BPDE binding on the conformational transition, induced by MnCl2 or NaCl, was also studied. The results obtained demonstrate that in Mn2+-containing solutions, when the ionic conditions are identical, there is only a minor difference in the extent of covalent binding of anti-BPDE to the polynucleotide in right- or left-handed form. A high degree of enantioselectivity of poly d[(G-C)(G-C)] towards (+)-anti-BPDE was observed with both conformational states, although the B form seems to be slightly more selective. With either form, the major adduct in the h.p.l.c. analysis is consistent with trans-N2-10-[(7 beta,8 alpha,9 alpha-trihydroxy-7,8,9,10- tetrahydrobenzo[a]pyrene)-yl]-deoxyguanosine [(+)-anti-BPDE-N2-dG] adducts. A 3 nm bathochromic shift of the light absorption of the pyrene chromophore was observed for the Mn2+-induced left-handed form of the polynucleotide. A similar shift was observed with the NaCl-induced transition only at intermediate NaCl concentrations, where the CD spectra showed a mixture of right- and left-handed forms. The bathochromic shift may be a consequence of a reduced exposure of the chromophore to the aqueous solvent. In poly d[(G-C)(G-C)] modified with anti-BPDE, higher ionic strengths are required to reach optimal B-Z transition compared to unmodified samples. This indicates that there is a restriction in the transition process at the sites of modification. The results have been discussed in terms of two distinct domains in the modified polynucleotide: one 'normal' domain, where an initially rapid transition takes place, and another 'BPDE-domain' involving the modification site and a few adjacent base pairs. It is likely that this domain is associated with the inhibitory effect on the B-Z transition.
