| 摘要 |
The present invention relates to compositions and methods for providing mitochondria-selective targeting agents covalently linked to desired cargo such as radical scavenging agents. Compositions and methods are disclosed for treating an illness that is caused or associated with cellular damage or dysfunction which is caused by excessive mitochondrial production of reaction oxygen species (ROS). Compositions which act as mitochondria-selective targeting agents using specific structural signaling features recognizable by cells as mitochondrial targeting sequences are discussed. A method for delivering these agents effectively into cells and mitochondria where they act as electron scavengers by way of certain targeting sequences is also disclosed. Mitochondria and cell death by way of apoptosis is inhibited as a result of the ROS-scavenging activity, thereby increasing the survival rate of the patient. In a preferred embodiment, the compositions and methods may be administered therapeutically in the field to patients with profound hemorrhagic shock so that survival could be prolonged until it is feasible to obtain surgical control of the bleeding vessels. In further preferred embodiments, the composition for scavenging radicals in a mitochondrial membrane includes a radical scavenging agent and a membrane active compound having a high affinity with said mitochondrial membrane and associated methods. In another embodiment, the cargo transported by mitochondrial-selective targeting agents may include an inhibitor of nitrous oxide system (NOS) enzyme activity.
|
