An absorption-emission system for the evaluation of DNA photocleaving agents

用于评估 DNA 光裂解剂的吸收发射系统

• 批准号: 345948-2007
• 负责人: McFarland, Sherri
• 金额: $ 10.82万
• 依托单位: Acadia University
• 依托单位国家: 加拿大
• 项目类别: Research Tools and Instruments - Category 1 (<$150,000)
• 财政年份: 2006
• 资助国家: 加拿大
• 起止时间: 2006-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=325922
• 关键词: absorption; emission; system; evaluation; DNA

Absorption and emission spectroscopy together permit the characterization of both ground and excited state molecular properties.  Once known, these properties constitute the optical signature of a molecule, and changes in this optical signature as a function of molecular environment provide a wealth of information regarding the nature of both electronic and molecular interactions.  Purchase of an absorption-emission spectroscopy system is proposed to  characterize the ground and excited state properties of new DNA photocleaving agents for use in photodynamic therapy (PDT), a treatment for certain cancers as well as age-related macular degeneration.  DNA photocleaving agents are artificial nucleases that introduce single- or double-strand breaks in the DNA backbone upon photoactivation with an appropriate wavelength of light.  The design of new agents must address current limitations:  (i) requirement for molecular oxygen to function, (ii) lack of double-strand cleaving capacity, and (iii) maximal absorption outside the phototherapeutic window (700-900 nm).  The proposed absorption-emission system is required to characterize fully the photophysical properties of new DNA photocleaving agents and to investigate their interactions with DNA.  This knowledge is essential to outlining the mechanistic aspects of new DNA photocleaving agents and evaluating their potential as candidates for PDT in the context of those limitations outlined previously.      This absorption-emission system is also required by four additional co-applicants.  Two of these are collaborators that wish to determine whether the cytotoxicity demonstrated by their designed molecules stems, in part, from direct interaction with the DNA backbone.  Co-applicants with unrelated research projects will use the instrument for fluorescence monitoring of environmental trace metals and absorption and fluorescence characterization of photocages.  The lack of dedicated absorption and fluorescence spectrometers for research in the Chemistry Department at Acadia University further necessitates the acquisition of the proposed absorption-emission system.

吸收光谱和发射光谱一起允许表征基态和激发态分子性质。一旦已知，这些性质就构成了分子的光学特征，以及作为分子环境的函数的这种光学特征的变化提供了关于电子和分子相互作用的性质的丰富信息。发射光谱系统被提出来表征用于光动力疗法（PDT）的新型DNA光切割剂的基态和激发态性质，用于治疗某些癌症以及与年龄相关的黄斑变性。DNA光切割剂是人工核酸酶，其引入单或双-在适当波长的光的光活化作用下，DNA骨架中的链断裂。新试剂的设计必须解决当前的限制：（i）需要分子氧发挥作用，（ii）缺乏双链切割能力，和（iii）光疗窗口外的最大吸收（700-900 nm）。建议的吸收-发射系统需要充分表征新的DNA光切割剂的生物物理性质并研究它们与DNA的相互作用。这些知识对于概述新的DNA光裂解剂的机制方面，并评估其作为PDT的候选人在这些限制的背景下，先前概述的潜力。 另外四个共同申请人也需要这种吸收-发射系统。其中两个是合作者，他们希望确定他们设计的分子所表现出的细胞毒性是否部分源于，直接与DNA骨架相互作用。申请人的研究项目不相关，将使用该仪器进行环境痕量金属的荧光监测，以及光笼的吸收和荧光表征。在哥伦比亚大学的化学系中缺乏用于研究的专用吸收和荧光光谱仪进一步需要获得所提出的吸收-发射系统。