與醣類鍵結之雙亞硝基鐵核錯合物

Sugar-Bound Dinitrosyl Iron Complex (DNIC)

周哲芳(Chou, Che Fang)

指導教授 ： 廖文峯

國立清華大學/理學院/化學系/碩士(2015年)

https://doi.org/10.6843/NTHU.2015.00098

摘要

摘要
　　在台灣，肝癌是目前死亡率第一名的癌症，當肝細胞不斷地異常分裂時，會形成癌化腫瘤進而演變成肝癌。已知在肝臟細胞膜上，具有去唾液酸醣蛋白受體( Asialoglycoprotein receptors, ASGP-R)，其可以辨識接有半乳糖( galactose)結構的化合物，使其順利進入肝臟內。此外，先前的文獻報導一氧化氮具有抑制癌細胞生長的功能，而雙亞硝基鐵化合物被認為生物體內一氧化氮的儲存者及提供者。因此開始嘗試合成具有半乳糖鍵結之雙亞硝基鐵化合物以達到辨認肝癌細胞進而釋放一氧化氮抑制其生長之專一性藥物，本實驗中， 以Fe(CO)2(NO)2作為起始物，與帶有乳醣分子( lactose)的disulfide反應，生成具水溶性且穩定性良好的{Fe(NO)2}9-{Fe(NO)2}9 [Fe(μ-S-C2- Lactose)(NO)2 ]2 ( Sugar RRE )，因醣類化合物水溶性高，不易得到晶體，無法藉由X-ray鑑定結構，因此利用紅外線光譜儀、高性能液相層析串聯質譜儀、電子順磁光譜儀以及紫外-可見光光譜儀來鑑定此化合物。同時以人類肝癌細胞(HePG-2)作為模型進行一系列的細胞實驗測試，期望此雙核之雙亞硝基鐵化合物所鍵結之乳醣可與 ASGP-R 有專一性結合，使RRE順利進入肝癌細胞後轉變為雙亞硝基鐵硫錯合物( DNICs )，釋放出一氧化氮，進而達到抑制肝癌細胞生長之目的。

關鍵字

雙亞硝基鐵核錯合物

並列摘要

Abstract
　　Hepatocellular carcinoma (HCC), also called Liver cancer, is the sixth most common cancer worldwide and the leading cause of death amongst cirrhotic patients.
Since there are asialoglycoprotein receptors, ASGP-R, in the surface of livers, ASGP-R can identify the structure of galactose. In this study, We tried to synthesize a lactose-bound compound, in order to drive the cancer-therapy compound into liver cells easily. Transformation of dinitrosyl iron complex (DNIC) [ Fe(CO)2(NO)2 ] into{Fe(NO)2}9-{Fe(NO)2}9 [Fe(μ-S-C2- Lactose)(NO)2 ]2 ( Sugar RRE ), triggered by Lactose-C2-Disulfide. The water solubility of Sugar RRE makes it difficult to get single-crystal X-ray structure, so the structure of Sugar RRE was validated by mass spectrum, infrared spectrum, UV-visible spectrometer and electron paramagnetic resonance (EPR).In series of assay, human liver cancer cell (HePG-2) was adopted as an experimental model . We expected that the binding of Sugar-RRE to ASGP-R is sospecific that RRE can penetrate into liver cancer cells easily, converted into DNICs and then release NO to kill liver cancer cells.

並列關鍵字

DNIC

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