Anchored Antioxidants to Provide Increased Protective Effect

描述(由申请人提供)：非常有说服力的数据表明，氧化应激是许多重大人类疾病的潜在组成部分，如糖尿病、心脏病、脑血管疾病(如中风)、周围血管疾病、神经退化(阿尔茨海默氏症、帕金森氏症、肌萎缩侧索硬化症和亨廷顿病)以及衰老。然而，到目前为止，抗氧化剂治疗减轻人类疾病的结果令人失望，氧气应激是其病理的一个基本组成部分。Tosk，Inc.成功地设计了一种试剂，可以将传统抗氧化剂不可逆地结合到位于活性氧物种形成区域的酶上。这样做是为了让传统的抗氧化剂更有效。现在，Tosk请求第一阶段SBIR资金，以进一步探索这种方法，以生产更活跃的抗氧化剂。总共将合成15种新型抗氧化剂，并在最初用于发现Tosk设计的新型抗氧化剂活性的同一动物模型中进行测试。其中三个合成的分子还将在另一个与过度氧化应激有关的人类疾病动物模型中进行测试，作为该疾病潜在病理的重要部分。 与公共卫生相关：到目前为止，抗氧化剂治疗减轻作为病理基础组成部分的氧气应激的人类疾病的结果令人失望。Tosk，Inc.成功地设计了一种试剂，可以将传统抗氧化剂不可逆地结合到位于活性氧物种形成区域的酶上。这样做是为了让传统的抗氧化剂更有效。现在，Tosk要求第一阶段SBIR资金进一步探索这一方法，以生产更活跃的抗氧化剂，并在另一个与过度氧化应激相关的人类疾病动物模型中评估该方法，作为病理基础的重要部分。

DESCRIPTION (provided by applicant): Very compelling data are available to suggest oxidative stress is an underlying component of many significant human diseases such as diabetes, heart disease, cerebrovascular disease (eg, stroke), peripheral vascular disease, neurodegeneration (Alzheimer's, Parkinson's, ALS and Huntington's disease) as well as aging. However, results to date with antioxidant treatments to mitigate human diseases with oxygen stress as an underlying component of the pathology have been disappointing. Tosk, Inc. has successfully designed an agent to irreversibly bind a traditional antioxidant to an enzyme located in the region where reactive oxygen species are formed. This was done to make the traditional antioxidant more effective. Now Tosk requests Phase I SBIR funding to further explore this approach to produce even more active antioxidants. A total of 15 novel antioxidants will be synthesized and tested in the same animal model used originally to discover the activity of the new antioxidant designed at Tosk. Three of the synthesized molecules will also be tested in one additional animal model of human disease associated with excess oxidative stress as a significant part of the condition's underlying pathology. PUBLIC HEALTH RELEVANCE: Results to date with antioxidant treatments to mitigate human diseases having oxygen stress as an underlying component of the pathology have been disappointing. Tosk, Inc. has successfully designed an agent to irreversibly bind a traditional antioxidant to an enzyme located in the region where reactive oxygen species are formed. This was done to make the traditional antioxidant more effective. Now Tosk requests Phase I SBIR funding to further explore this approach to produce more active antioxidants as well as to evaluate the approach in one additional animal model of human disease associated with excess oxidative stress as a significant part of the conditions underlying the pathology.