SuFEx: a metal-free click ligation for multivalent biomolecules.

Area of Science:

• Organic Chemistry
• Click Chemistry
• Bioconjugation

Background:

• Sulfur(VI) fluoride exchange (SuFEx) is an emerging click reaction with broad synthetic utility.
• SuFEx is based on the high reactivity of sulfonyl fluorides and fluorosulfates with nucleophiles.

Purpose of the Study:

• To explore the application of SuFEx in synthesizing novel sugar-containing sulfonamides.
• To demonstrate SuFEx utility in creating multivalent scaffolds and functionalizing proteins.

Main Methods:

• Reaction of glycosylsulfonyl fluoride with aliphatic amines for sugar sulfonamide synthesis.
• Application of SuFEx to tetraamino- and tetrafluorosulfonyl-calixarene scaffolds.
• Chemoselective functionalization of bovine serum albumin (BSA) using SO2F2.
• PEGylation of BSA using a PEG-fluorosulfate.

Main Results:

• Successful synthesis of a new family of sugar sulfonamides.
• Creation of sulfonamide-linked sugar and iminosugar clusters on multivalent scaffolds.
• Generation of a multivalent BSA-SO2F system via lysine functionalization.
• Demonstration of BSA PEGylation using SuFEx.

Conclusions:

• SuFEx is a powerful tool for synthesizing diverse sulfonamide-containing molecules, including complex carbohydrate structures.
• SuFEx enables efficient bioconjugation, allowing for protein modification and the creation of functional protein-based materials.