Synthetic study on selenocystine-containing peptides

Area of Science:

• Organic Chemistry
• Peptide Chemistry
• Biochemistry

Background:

• Solid-phase peptide synthesis (SPPS) is a cornerstone of peptide production.
• Incorporating non-canonical amino acids like selenocysteine offers unique chemical properties.
• Developing stable and efficiently deprotected selenocysteine building blocks is crucial for expanding SPPS capabilities.

Purpose of the Study:

• To synthesize and characterize a novel Fmoc-protected selenocysteine derivative, Fmoc-Sec(MBzl)-OH.
• To evaluate the utility of Fmoc-Sec(MBzl)-OH in Fmoc-based SPPS.
• To investigate the formation and stability of peptide diselenide bonds derived from this building block.

Main Methods:

• Synthesis of N-9-Fluorenylmethoxycarbonyl-Se-4-methoxybenzylselenocysteine [Fmoc-Sec(MBzl)-OH] from selenocystine.
• Application of Fmoc-Sec(MBzl)-OH in Fmoc-based solid-phase peptide synthesis.
• Chemical treatment with iodine or DMSO-TFA for diselenide bond formation.
• Comparative kinetic studies of diselenide and disulfide reduction using reduced glutathione.

Main Results:

• Successful synthesis and application of Fmoc-Sec(MBzl)-OH in SPPS.
• Demonstrated stability and defined deprotection conditions for the Se-MBzl group.
• Efficient direct formation of peptide diselenide bonds between Sec(MBzl) residues.
• Comparative analysis of reduction kinetics revealed differences between diselenide and disulfide bonds.

Conclusions:

• Fmoc-Sec(MBzl)-OH is a valuable building block for Fmoc-based SPPS.
• The Se-MBzl protecting group offers stability and facilitates efficient diselenide bond formation.
• Peptide diselenide bonds can be readily formed and offer distinct properties compared to disulfide bonds.