Preparation of Molecular Aptamer Conjugated Nanomaterials for Control the Activity of Enzyme and Drug Development

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Project title

Code/計畫編號

NSC99-2113-M019-001-MY2

Translated Name/計畫中文名

分子適合體修飾的奈米材料於蛋白質酵素控制與藥物開發

Project Coordinator/計畫主持人

Chih-Ching Huang

Funding Organization/主管機關

National Science and Technology Council

Department/Unit

Department of Bioscience and Biotechnology

Website

https://www.grb.gov.tw/search/planDetail?id=2205225

Year

2011

Start date/計畫起

01-08-2011

Expected Completion/計畫迄

31-07-2012

Bugetid/研究經費

2275千元

ResearchField/研究領域

化學
生物技術(理)
藥學

"本計畫之目標是結合適合體與金奈米粒子於凝血酶酵素控制與抗凝血劑藥物開發。適合體相較於傳統抗體有易製備、易修飾、易保存、分子量低和少免疫反應等優點。但有些篩選出分子適合體對目標分子的結合力較弱。我們主要利用凝血酶適合體修飾於金奈米粒子後，因有兩種以上的適合體被篩選出結合於凝血酶上的不同位置，故經由多重結合 (multivalent binding)效應來增強與目標凝血酶結合常數，進而增強抑制凝血的效率。本計畫將提出奈米粒子表面自排列/自我組裝的技術，並與傳統自我組裝技術比較。利用適合體互補DNA 修飾的金奈米粒子或搭配雷射照光反應，期望能回復被抑制凝血酶的活性，達到藥物控制凝血的目的。" "The goal of this proposal is preparation of aptamer conjugated nanoparticles for efficiently control the activity of thrombin. Aptamers have emerged as a powerful class of ligands for specific biomolecular targeting and can rival the merits of other molecular probes due to their unique properties, such as the ease of synthesis, manipulation and storge, small sizes, and lack of immunogenicity. However, there are some obstacles which limit their capabilities for high efficiently binding to target molecules. For example, some of the selected aptamers possess weak binding affinity. Gold nanoparticles conjugated with thrombin-binding aptamer (TBA-Au NPs) are proposed effectively control the activity of thrombin toward fibrinogen. We also try to investigate the Au NPs-based self-assembly monolayer (SAM) and self-arrangement/-assembly monolayer (SAAM) methods in the control of activity of thrombin. Restoration of the activity of thrombin by aptamer-modified nanoparticles and femtosecond-Laser irradiation allow us to develop antidote drugs. The anticoagulant activity of the TBA-Au NPs was suppressed by laser irradiation or cTBA-Au NPs that prepared by Au NPs modified with TBA-complementary sequences (cTBA27). Because the preparation of the TBA27-Au NPs and cTBA27-Au NPs is simple and cost-effective, they hold great potential for use in biomedical applications, particularly for treating various diseases related to blood clotting disorders. This study opens the possibility of using aptamer-functionalized nanomaterials to regulate molecular binding, protein recognition, and enzyme activity."

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Preparation of Molecular Aptamer Conjugated Nanomaterials for Control the Activity of Enzyme and Drug Development

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