On-resin multicomponent protocols for biopolymer assembly and derivatization.

Area of Science:

• Organic Chemistry
• Polymer Chemistry
• Biochemistry

Background:

• Solid-phase synthesis is key for automated biomolecule production.
• Traditional solid-phase methods lack functional diversity beyond building blocks.
• Multicomponent reactions (MCRs) offer rapid diversity generation.

Purpose of the Study:

• To review on-resin MCRs for biopolymer modification.
• To highlight MCRs' utility in creating complex peptide and oligonucleotide libraries.
• To provide practical guidance for implementing solid-supported MCR protocols.

Main Methods:

• On-resin multicomponent reactions (MCRs) for biopolymer derivatization.
• Solid-phase synthesis techniques for peptides, nucleic acids, and polysaccharides.
• Application of MCRs in lipidation, biotinylation, labeling, and ligation.

Main Results:

• Demonstrated MCRs for diverse covalent modifications on peptides and oligonucleotides.
• Showcased MCRs for traceless on-resin synthesis of cyclic peptides and hybrid architectures.
• Illustrated MCRs in DNA-encoded library technology.

Conclusions:

• On-resin MCRs significantly expand biopolymer modification capabilities.
• Solid-supported MCRs enable synthesis of complex structures not feasible in solution.
• This review offers practical insights for utilizing MCRs in solid-phase biopolymer synthesis.