Sustainable Peptide Synthesis Enabled by a Transient Protecting Group

Area of Science:

• Synthetic Chemistry
• Green Chemistry
• Biochemistry

Background:

• Current synthetic peptide production relies heavily on toxic organic solvents.
• Developing environmentally friendly peptide synthesis methods is crucial for sustainability.
• Water as a reaction medium presents significant challenges in traditional peptide chemistry.

Purpose of the Study:

• To develop a sustainable and aqueous-based solid-phase peptide synthesis (SPPS) strategy.
• To introduce a novel water-compatible protecting group for amino acids.
• To enable efficient peptide assembly in an environmentally benign reaction medium.

Main Methods:

• Development of the 2,7-disulfo-9-fluorenylmethoxycarbonyl (Smoc) protecting group, compatible with aqueous conditions.
• Synthesis of natural and non-natural Smoc-protected amino acids.
• Application of the Smoc strategy in aqueous solid-phase peptide synthesis for assembling 22 peptide sequences.

Main Results:

• Demonstration of successful peptide assembly under aqueous conditions using the Smoc protecting group.
• Real-time monitoring of building block coupling was achieved.
• Efficient postsynthetic purification of synthesized peptides was performed.
• Evaluation of fundamental SPPS issues including protecting group strategy, coupling/cleavage efficiency, and stability in water.

Conclusions:

• The novel aqueous SPPS strategy using the Smoc protecting group offers a sustainable alternative to traditional methods.
• This approach facilitates greener peptide synthesis by eliminating toxic solvents.
• The Smoc strategy is versatile, enabling the synthesis of various peptide sequences under mild, aqueous conditions.