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首页> 外文期刊>Biochemistry >DNA Binding Characteristics of Mithramycin and Chromomycin Analogues Obtained by Combinatorial Biosynthesis
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DNA Binding Characteristics of Mithramycin and Chromomycin Analogues Obtained by Combinatorial Biosynthesis

机译：组合生物合成获得的光神霉素和铬霉素类似物的DNA结合特征

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摘要

The antitumor antibioticsmithramycin A and chromomycin A3 bind reversibly to theminor groove ofnG/C-rich regions in DNA in the presence of dications such as Mg2þ, and their antiproliferative activity hasnbeen associated with their ability to block the binding of certain transcription factors to gene promoters.nDespite their biological activity, their use as anticancer agents is limited by severe side effects. Therefore, innour pursuit of new structurally related molecules showing both lower toxicity and higher biological activity,nwe have examined the binding to DNA of six analogues that we have obtained by combinatorial biosyntheticnprocedures in the producing organisms.All thesemolecules bear a variety of changes in the side chain attachednto C-3 of the chromophore. The spectroscopic characterization of their binding to DNA followed by thenevaluation of binding parameters and associated thermodynamics revealed differences in their bindingnaffinity. DNA binding was entropically driven, dominated by the hydrophobic transfer of every compoundnfrom solution into the minor groove of DNA. Among the analogues, mithramycin SDK and chromomycinnSDK possessed the higher DNA binding affinities.
机译：在有诸如Mg2 +之类的药物存在下，抗肿瘤抗生素铁匠霉素A和嗜铬霉素A3可逆地与DNA中富含nG / C的区域的小沟可逆结合，它们的抗增殖活性与它们阻断某些转录因子与基因启动子结合的能力有关。 n尽管其具有生物活性，但其作为抗癌剂的使用受到严重副作用的限制。因此，为了追求既显示出较低的毒性又显示出更高的生物活性的新的结构相关分子，我们研究了在生产生物体中通过组合生物合成过程获得的六种类似物与DNA的结合。所有这些分子在侧面都具有多种变化。链连接在发色团的C-3上。其与DNA结合的光谱表征，然后评估结合参数和相关的热力学，揭示了它们结合亲和力的差异。 DNA结合是熵驱动的，主要是每种化合物从溶液向DNA的小沟中的疏水转移。在类似物中，光神霉素SDK和嗜铬霉素SDK具有较高的DNA结合亲和力。

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  • 来源
    《Biochemistry》 |2010年第49期|p.10543-10552|共10页
  • 作者

    Francisca Barcel Miguel Ortiz-Lombarda Miquel Martorell Miquel Oliver Carmen Mndez Jos A. Salas and Jos Portugal;

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    ‡Departament de Biologia Fundamental i Ciencies de la Salut, Universitat de les Illes Balears, Palma de Mallorca, Spain,§Architecture et Fonction desMacromolu0001 ecules Biologiques (UMR6098), CNRS, Universitu0001 es d’Aix-Marseille I & II,Marseille, France,) Departamento de Biologia Funcional-Instituto Universitario de Oncologia del Principado de Asturias, Oviedo, Spain, and^Instituto de Biologia Molecular de Barcelona, CSIC, Parc Cientific de Barcelona, Barcelona, Spain;

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