Mussel derived radical scavenging peptide (MSRP) is a natural antioxidant that contains two Histidine residues. It has been shown to scavenge superoxide, hydroxyl, and carbon-centered radicals and can inhibit lipid peroxidation. In addition, it been shown to chelate Fe<sup>2+</sup> ions. In this study, we aim to enhance the antioxidant and metal chelating properties of MSRP by synthesizing a mutant derivative of this peptide that contains the non-natural amino acid 2-thioHistidine (2-thioHis), in place of MSPR’s histidine residues using Solid Phase Peptide Synthesis (SPPS). 2-thioHis is the amino acid derivative of Ergothioneine (EGT). EGT is a small molecule produced by fungi and actinobacteria. EGT, which humans obtain through diet, has been shown to accumulate in several vital organ systems and is thought to be essential since deficiencies result in neurological and cardiovascular disorders. EGT has been shown to have antioxidant and metal chelation properties <i>in vitro</i> but the full scope of its biological functions remains unknown. Despite the biological importance of EGT, it has only been incorporated into peptides (as its 2-thioHis derivative) in three previous studies. Herein, we report the synthesis of acyl-activated derivatives of 2-thioHis that are suitable for SPPS. We also focus on incorporating our 2-thioHis derivatives into the MSRP peptide and exploring its biochemical activities. We predict that our MSRP mutant will have enhanced radical scavenging, antioxidant, and metal chelation properties due to the presence of 2-thioHis.

Synthesis of Ergothioneine derivatives and incorporation into MSRP peptide

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