SYNTHETIC SUBSTRATES FOR ENZYMES THAT CATALYZE REACTIONS OF MODIFIED CYSTEINES AND RELATED METHODS
申请人:The University of Chicago
公开号:US20180147250A1
公开(公告)日:2018-05-31
Synthetic probes for detecting the activity of enzymes that catalyze reactions of post-translationally modified cysteine residues are described. The probes include “turn-on” probes that include a carbamate linkage that is cleaved via an intramolecular reaction with a free thiol produced by an enzyme catalyzed activity. The probes also include ratiometric, Michael addition-based probes that respond to enzymatic activity by a change in structure that results in a change in fluorescence properties. Methods of using the probes to detect enzymatic activity and disease are described. For example, the probes can be used to detect enzymatic activity in a variety of samples, including live cells and heterogeneous tissues. In addition, prodrugs that can be activated by enzymes that catalyze reactions of post-translationally modified cysteine residues and methods of using the prodrugs to treat disease are described.
描述了用于检测催化后翻译修饰半胱氨酸残基反应活性的酶的合成探针。这些探针包括“开启”探针,其中包括通过酶催化活性产生的游离巯基进行分子内反应从而裂解的碳酸酯连接。这些探针还包括比例计量、基于迈克尔加成的探针,通过结构的变化响应酶活性,导致荧光特性的变化。描述了使用这些探针检测酶活性和疾病的方法。例如,这些探针可用于检测各种样本中的酶活性,包括活细胞和异质组织。此外,还描述了可以由催化催化后翻译修饰半胱氨酸残基反应的酶激活的前药和使用这些前药治疗疾病的方法。