Characterization of SS-31 analogues containing the unique amino acid 2-thiohistidine
Abstract
The mitochondrial-targeted, antioxidant peptide SS-31 (dArg-Dmt-Lys-Phe) has found use as a therapeutic to protect mitochondria from lipid peroxidation. It targets cardiolipin (CL), an abundant lipid of the inner mitochondrial membrane. The antioxidant residue within the peptide is dimethyltyrosine (Dmt). Here, 2-thiohistidine (2TH), an analogue of ergothioneine, was used as a replacement for Dmt to test for improved antioxidant function. A first generation of peptides was synthesized by replacing the Dmt residue with 2TH to give the sequence dArg-2TH-Lys- Phe. A second generation of peptides included an additional antioxidant residue attached at the N terminus, generating Dmt-dArg-Dmt-Lys-Phe, peptide Dmt-dArg-2TH-Lys-Phe, and 2TH-dArg- 2TH-Lys-Phe.
Primary Faculty Mentor Name
Robert Hondal
Status
Undergraduate
Student College
College of Arts and Sciences
Program/Major
Chemistry
Primary Research Category
Physical Science
Characterization of SS-31 analogues containing the unique amino acid 2-thiohistidine
The mitochondrial-targeted, antioxidant peptide SS-31 (dArg-Dmt-Lys-Phe) has found use as a therapeutic to protect mitochondria from lipid peroxidation. It targets cardiolipin (CL), an abundant lipid of the inner mitochondrial membrane. The antioxidant residue within the peptide is dimethyltyrosine (Dmt). Here, 2-thiohistidine (2TH), an analogue of ergothioneine, was used as a replacement for Dmt to test for improved antioxidant function. A first generation of peptides was synthesized by replacing the Dmt residue with 2TH to give the sequence dArg-2TH-Lys- Phe. A second generation of peptides included an additional antioxidant residue attached at the N terminus, generating Dmt-dArg-Dmt-Lys-Phe, peptide Dmt-dArg-2TH-Lys-Phe, and 2TH-dArg- 2TH-Lys-Phe.
