Multicomponent Reactions in Ligation and Bioconjugation Chemistry

Area of Science:

• Synthetic Organic Chemistry
• Bioconjugation Chemistry
• Medicinal Chemistry

Background:

• Multicomponent reactions (MCRs) are efficient synthetic strategies for creating complex molecules in a single step.
• Their application in biomolecular construct preparation is a recent and rapidly developing field.
• MCRs offer advantages in complexity generation and synthetic cost reduction.

Purpose of the Study:

• To review the utilization of MCRs for the ligation and conjugation of biomolecules.
• To highlight the group's contributions and validate MCRs as a bioconjugation strategy.
• To encourage the application of MCRs in novel biomedicinal challenges.

Main Methods:

• Utilizing isocyanide-based MCRs for glycolipid synthesis.
• Applying MCRs for solution-phase and solid-phase peptide lipidation and labeling.
• Employing MCRs for protein labeling, modification, immobilization, and glycoconjugation.
• Demonstrating multicomponent polysaccharide-protein conjugation for vaccine development.

Main Results:

• MCRs efficiently ligate lipids, steroids, carbohydrates, and tags to peptides and proteins.
• One-pot double lipidation of glycan fragments and simultaneous peptide lipidation/biotinylation were achieved.
• MCRs enable synchronized lipidation/labeling and macrocyclization of peptides.
• Successful multicomponent polysaccharide-protein conjugation yielded multivalent glycoconjugate vaccine candidates.

Conclusions:

• MCRs are powerful and versatile tools for diverse biomolecular conjugation and modification.
• This approach significantly simplifies the synthesis of complex bioconjugates.
• MCRs hold great promise for advancing drug discovery, diagnostics, and therapeutic development.