Peptide synthesis using novel S-sulfocysteine derivatives

Area of Science:

• Organic Chemistry
• Biochemistry
• Peptide Chemistry

Background:

• Cysteine modification is crucial for peptide synthesis.
• Developing stable cysteine derivatives is essential for efficient peptide production.
• Solid-phase peptide synthesis (SPPS) requires robust protecting groups and intermediates.

Purpose of the Study:

• To synthesize novel cysteine S-sulfonate derivatives.
• To evaluate the utility of these derivatives in peptide synthesis, specifically SPPS.
• To assess the stability of the S-sulfonate group during SPPS.

Main Methods:

• Preparation of Boc-Cys(SO3Na)-ONa and Fmoc-Cys(SO3Na)-ONa.
• Solid-phase peptide synthesis of Arg8-vasopressin using the Fmoc derivative.
• Utilizing the Bunte salt intermediate (7) for peptide coupling.
• Employing p-cresol as a scavenger during resin cleavage.
• Purification of intermediate 7 via ion-exchange chromatography.
• Cleavage of the S-sulfonate group using tributylphosphine.

Main Results:

• Successful synthesis of two new cysteine S-sulfonate derivatives.
• Demonstrated utility of Fmoc-Cys(SO3Na)-ONa in the SPPS of Arg8-vasopressin.
• Observed good stability of the S-sulfonate group under SPPS conditions with p-cresol scavenging.
• Purification of the Bunte salt intermediate was achieved via ion-exchange chromatography.

Conclusions:

• The novel cysteine S-sulfonate derivatives, particularly the Fmoc variant, are suitable for peptide synthesis.
• The S-sulfonate group exhibits adequate stability during SPPS when appropriate scavenging methods are used.
• This work provides a valuable tool for incorporating modified cysteine residues into peptides.