遠距、側翼殘基對棘黴素與核酸複合物結構之影響

The effects to the structure of echinomycin-DNA complex by distant and flanking residues

王立翔(Li-Shiang Wang)

指導教授 ： 黃文彰 博士

國立臺灣師範大學/理學院/化學系/碩士(1999年)

摘要

棘黴素是quinoxaline族中具有抗腫瘤功效之藥物。利用化學足跡法發現，棘黴素對於以d(CG)為中心之序列具有最好之結合能力。到目前為止，對此複合物的結構生物學研究，多半針對迴文對稱週邊序列的DNA做探討，以降低其複雜性。但由於棘黴素本身並非完全對稱的結構，因此乃探討非迴文對稱週邊序列DNA與棘黴素結合成複合物後，是否會有不同結構的複合物生成。本文採用[d(TACCGCAT)•d(ATGCGGTA)](簡稱CG8)的不對稱序列DNA做探討，並與之前做過[d(CCGC)•d(GCGG)](簡稱CG4)序列比較。和CG4與棘黴素所生成的複合物相比，CG8和棘黴素亦生成兩組穩定複合物。整個複合物仍以氫鍵、凡得瓦力和鹼基間堆疊作用力來穩定結構，其中以堆疊作用力更為重要。在結構方面，發現DNA和棘黴素結合後會有鬆開的現象，遠距及側翼殘基彼此間距離變短，類似A-form DNA。藥物插入部分的醣基會比較傾向A-form DNA，遠距殘基則維持B-form形式。和CG4複合物相比，整體結構更偏於B-form的形式。

關鍵字

棘黴素 ； 複合物結構

並列摘要

Echinomycin, a member of quinoxaline family drug is a potent antibiotic and antitumor agents. It is probably the most well
defined model system in terms of the binding sites specificity. It is however, all of the structural studies up to present were focused
on the palindromic DNA sequence, Nevertheless, the only model can reveal the nature of binding specificity is to use a non-
palindromic binding sites by realizing the lacking of an exact two-fold symmetry of echinomycin molecule itself. Here, we
investigate the echinomycin-bound complex structure of a longer sequence, namely [d(TACCGCAT)•d(ATGCGGTA)], and to be compared with a previous studied shorter sequence, namely [d(CCGC)•d(GCGG)]. The effects to the fine structural modification of
echinomycin-DNA complex by distant and flanking residues as well as its distinct structural features are addressed in detail.

並列關鍵字

echinomycin ； structure of complex

參考文獻

Altona, C. & Sundalingam, M. (1972) J. Amer. Chem. Soc. 8205-8211.

Addess K. J. & Feigon J. (1994a) Biochemistry 33, 12386-12396.

Addess K. J. & Feigon J. (1994b) Biochemistry 33, 12397-12404.

J. Mol. Biol. 215, 411-428.

Biochemistry 32, 8702-8711.