Compounds for delivering amino acids or peptides with antioxidant activity into mitochondria and use thereof

• US 20060160748A1
• Filed: 12/20/2005
• Published: 07/20/2006
• Est. Priority Date: 11/25/2003
• Status: Abandoned Application

• Current Assignee: University of Rochester
• Original Assignee: University of Rochester
• Inventors: Nauduri, Dhananjaya, Xu, Lin, Sharma, Virendra K., Anders, Marion W., Sheu, Shey-Shing
• Application Number:
  US11/312,873
• Publication Number:
  US 20060160748A1
• Time in Patent Office: Days
• US Class Current: 514/15.100
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 38/063 Glutathione

Abstract

Disclosed are compounds containing single amino acids, peptides, or derivatives thereof which are selectively delivered to the mitochondria of a cell. Compounds of the invention exhibit antioxidant activity thereby reducing reactive oxygen species in cells. These compounds are useful for inhibiting oxidative stress-induced cell injury or death both in vivo and ex vivo. In addition, methods for the synthesis of these compounds are disclosed.

Claims

1. An amino acid-based antioxidant compound selectively delivered into the mitochondria of a cell.

2. A pharmaceutical composition comprising the antioxidant of claim 1 in admixture with a pharmaceutically acceptable carrier.

3. A method for producing a compound of claim 1 comprising linking an amino acid-based antioxidant to a delivery moiety which selectively delivers the antioxidant to the mitochondria of a cell.

4. A method of inhibiting oxidative stress-induced cell injury or death comprising contacting a cell with the compound of claim 1, whereby the compound is taken up by the cell and is selectively delivered into the mitochondria of the cell, thereby scavenging oxidative free radicals or reactive oxygen species to inhibit oxidative stress-induced cell injury or death.

5. A method of treating a condition associated with oxidative stress-induced cell injury or death comprising administering an effective amount of the composition of claim 2 to a patient having a condition associated with oxidative stress-induced cell injury or death, whereby the compound is taken up by cells at risk of oxidative stress-induced injury or death, and is selectively delivered into the mitochondria of the cells to inhibit oxidative stress-induced injury or death thereof, thereby treating the condition.