(PQA4) Detecting carcinogens in complex environments via energy transfer

描述(由申请人提供)：这项提案的主要目标是开发一种新的致癌化合物传感器，使用商业上可获得的无毒大环伽马-环糊精。环糊精将结合其内腔中的致癌物，以及一种明亮的荧光小分子染料。一旦这两个分子结合在空腔中，它们就会足够近，以至于激发致癌物将导致能量转移到染料并从染料发出明亮的荧光。与以前开发的传感器相比，这里提出的传感器具有许多优点，包括：(A)在存在其他化合物的情况下对致癌物具有高选择性；(B)能够在低浓度下检测致癌物的高灵敏度；(C)易于调谐，能够通过添加不同的染料来调谐荧光发射信号；以及(D)在一系列复杂的环境条件下对不同类别的致癌物具有高度的通用性。这项建议的生物医学相关性很明显：准确评估个人接触小分子致癌物的水平将有助于科学家确定患者患癌症的风险。

DESCRIPTION (provided by applicant): The broad goal of this proposal is to develop a new sensor for carcinogenic compounds, using a commercially available, non-toxic macrocycle, gamma-cyclodextrin. The cyclodextrin will bind carcinogens in its interior cavity, together with a brightly fluorescent small-molecule dye. Once the two molecules are bound in the cavity, they will be close enough so that exciting the carcinogen will result in energy transfer to and bright fluorescent emission from the dye. The sensor proposed herein has a number of advantages compared to previously- developed sensors, including: (a) high selectivity for carcinogens in the presence of other compounds; (b) high sensitivity that will enable the detection of carcinogens at low concentrations; (c) ease of tunability that will enable the tuning of the fluorescent emission signal by adding different dyes; and (d) high generality for different classes of carcinogens under a range of complex environmental conditions. The biomedical relevance of this proposal is clear: accurately assessing individuals' exposure levels to small-molecule carcinogens will aid scientists in determining patient's risk of developing cancer.