Jiménez-García E, Portugal J
Departamento de Bioquímica y Fisiologia, Facultad de Química, Universidad de Barcelona, Spain.
Biochemistry. 1992 Nov 24;31(46):11641-6. doi: 10.1021/bi00161a051.
The interaction of poly[(G-C)] and poly[d(G-m5C)] with the antitumor antibiotic elsamicin A, which binds to alternating guanine + cytosine tracts in DNA, has been studied under the B and Z conformations. Both the rate and the extent of the B-to-Z transition are diminished by the antibiotic, as inferred by spectroscopic methods under ionic conditions that otherwise favor the left-handed conformation of the polynucleotides. Moreover, elsamicin converts the Z-form DNA back to the B-form. The circular dichroism data indicate that elsamicin binds to poly[d(G-C)] and poly[d(G-m5C)] to form a right-handed bound elsamicin region(s). The transition can be followed by changes of the molar ellipticity at 250 nm, thus providing a convenient wavelength to monitor the Z-to-B conformational change of the polymers as elsamicin is added. The elsamicin A effect might be explained by a model in which the antibiotic binds preferently to a B-form DNA, playing a role as an allosteric effector on the equilibrium between the B and Z conformations, thus favoring the right-handed one.
已在B构象和Z构象下研究了聚[(G-C)]和聚[d(G-m⁵C)]与抗肿瘤抗生素埃沙米星A的相互作用,埃沙米星A与DNA中的交替鸟嘌呤+胞嘧啶序列结合。如通过光谱方法在离子条件下推断的那样,抗生素会降低B-Z转变的速率和程度,否则这种离子条件有利于多核苷酸的左手构象。此外,埃沙米星可将Z型DNA转变回B型。圆二色性数据表明,埃沙米星与聚[d(G-C)]和聚[d(G-m⁵C)]结合形成右手结合的埃沙米星区域。该转变可通过250nm处摩尔椭圆率的变化来跟踪,因此当加入埃沙米星时,这提供了一个方便的波长来监测聚合物的Z-B构象变化。埃沙米星A的作用可能由一种模型来解释,即抗生素优先与B型DNA结合,作为B构象和Z构象之间平衡的变构效应物发挥作用,从而有利于右手构象。