کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1233453 1495235 2014 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Spectroscopic detection of etoposide binding to chromatin components: The role of histone proteins
ترجمه فارسی عنوان
تشخیص اسپکتروسکوپی اتصال اتووزید به اجزای کروماتین: نقش پروتئین های هیستون
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
چکیده انگلیسی


• Structural alteration of chromatin upon etoposide binding.
• Higher affinity of etoposide to histone H1 compared to chromatin and DNA.
• Binding of etoposide to histone proteins increases the α-helical contents.
• Etoposide intercalated into DNA base pairs and quenches tyrosine residues of the histones.

Chromatin has been introduced as a main target for most anticancer drugs. Etoposide is known as a topoisomerase II inhibitor, but its effect on chromatin components is unknown. This report, for the first time, describes the effect of etoposide on DNA, histones and DNA–histones complex in the structure of nucleosomes employing thermal denaturation, fluorescence, UV absorbance and circular dichroism spectroscopy techniques. The results showed that the binding of etoposide decreased UV absorbance and fluorescence emission intensity, altered secondary structure of chromatin and hypochromicity was occurred in thermal denaturation profiles. The drug exhibited higher affinity to chromatin compared to DNA. Quenching of drug chromophores with tyrosine residues of histones indicated that globular domain of histones is the site of etoposide binding. Moreover, the binding of etoposide to histones altered their secondary structure accompanied with hypochromicity revealing compaction of histones in the presence of the drug. From the results it is concludes that apart from topoisomerase II, chromatin components especially its protein moiety can be introduced as a new site of etoposide binding and histone proteins especially H1 play a fundamental role in this process and anticancer activity of etoposide.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy - Volume 133, 10 December 2014, Pages 292–299
نویسندگان
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