Masked h-ANG variant conjugates useful for protection of cells, particularly neuronal cells from injury and death, particularly from injury and death associated with ROS (reactive oxygen species). Masked h-Ang variant conjugates do not exhibit ribonucleolytic activity until unmasked. Masked h-ANG variant conjugates are activatable by reaction with ROS and exhibit ribonucleolytic activity only after reaction with ROS. Masked h-ANG variant conjugates are useful in the treatment of neurodegenerative diseases and disorders, such as amyotrophic lateral sclerosis. Certain h-ANG variants in which lysine at position 40 is replaced with cysteine are provided at least as starting materials for making masked h-ANG variant conjugates. Certain h-ANG variants in which lysine at position 40 is replaced with thialysine are generated on unmasking of h-ANG variant conjugates and exhibit ribonucleolyitc activity.
掩蔽的h-ANG变体共轭物对细胞的保护有用,特别是对神经元细胞免受与ROS(活性氧化物质)相关的损伤和死亡的保护。掩蔽的h-ANG变体共轭物在未揭露之前不表现
核糖核酸酶活性。与ROS反应后,掩蔽的h-ANG变体共轭物可以被激活,并且仅在与ROS反应后才表现
核糖核酸酶活性。掩蔽的h-ANG变体共轭物在治疗神经退行性疾病和紊乱,如肌萎缩侧索硬化症方面是有用的。某些h-ANG变体,其中赖
氨酸在位置40被半胱
氨酸取代,至少作为制备掩蔽的h-ANG变体共轭物的起始材料提供。某些h-ANG变体,其中赖
氨酸在位置40被
硫赖
氨酸取代,是在揭露h-ANG变体共轭物时生成的,并表现
核糖核酸酶活性。