Solid Phase Synthesis

Overview

Source: Vy M. Dong and Diane Le, Department of Chemistry, University of California, Irvine, CA

Merrifield's solid-phase synthesis is a Nobel Prize winning invention where a reactant molecule is bound on a solid support and undergoes successive chemical reactions to form a desired compound. When the molecules are bound to a solid support, excess reagents and byproducts can be removed by washing away the impurities, while the target compound remains bound to the resin. Specifically, we will showcase an example of solid-phase peptide synthesis (SPPS) to demonstrate this concept.

Procedure

1. Loading the Resin

To a 100mL peptide synthesis vessel, add 2-chlorotrityl chloride (CTC) resin (1.1 mmol/g, 0.360 g, 0.400 mmol). Add 20 mL DMF and allow them to swell for 30 min under N_2.
Drain the beads under vacuum and add 10 mL DMF.
Add 500 mg Fmoc-Ala-OH (1.60 mmol) and 2.5 mL i-Pr₂EtN, and mix under N₂ for 15 min.
Drain the solvent under vacuum and repeat the loading with Fmoc-Ala-OH for 15 min.
Drain the solvent under

Results

Representative results for solid phase peptide synthesisfor Procedure 3.

Procedure Step	Color of solution
3.1	Control - Clear, light yellow Reaction – Clear, light yellow
3.2	Control - Clear, light yellow Reaction – Dark blue
3.3	Dark blue solution, beads blue – c Log in or to access full content. Learn more about your institution’s access to JoVE content here Application and Summary In this experiment, we have demonstrated an example of solid-phase synthesis via SPPS through the synthesis of a dipeptide. Solid-phase synthesis is widely used in combinatorial chemistry to build up libraries of compounds for rapid screening. It has been commonly used to synthesize peptides, oligosaccharides, and nucleic acids. Moreover, this concept has been implemented in chemical synthesis. Because it is heterogeneous, these solid-supported reagents can often be recycled and reused in subs Log in or to access full content. Learn more about your institution’s access to JoVE content here Tags Solid Phase Synthesis Method Synthesized Bound Insoluble Material Biological Oligomers Polymers Peptides Nucleic Acids Oligosaccharides Chains Monomers Correct Order Multi step Syntheses Purification Isolation Stable Products Intermediate Products Overall Yield Solid Support Solution phase Reagents Solvents Byproducts Washed Away Purify Isolate Steps Solid phase Peptide Synthesis Applications In Chemistry Skip to... 0:04 Overview 1:24 Principles of Solid Phase Synthesis 3:54 Amino Acid Loading and Deprotection 6:13 Peptide Coupling and Isolation 8:02 Applications 9:15 Summary Videos from this collection: Now Playing Solid Phase Synthesis Organic Chemistry II 40.0K Views Cleaning Glassware Organic Chemistry II 120.6K Views Nucleophilic Substitution Organic Chemistry II 97.8K Views Reducing Agents Organic Chemistry II 42.5K Views Grignard Reaction Organic Chemistry II 147.6K Views <em>n</em>-Butyllithium Titration Organic Chemistry II 46.9K Views Dean-Stark Trap Organic Chemistry II 97.1K Views Ozonolysis of Alkenes Organic Chemistry II 66.1K Views Organocatalysis Organic Chemistry II 16.3K Views Palladium-Catalyzed Cross Coupling Organic Chemistry II 33.2K Views Hydrogenation Organic Chemistry II 48.0K Views Polymerization Organic Chemistry II 89.7K Views Melting Point Organic Chemistry II 145.0K Views Infrared Spectroscopy Organic Chemistry II 205.0K Views Polarimeter Organic Chemistry II 97.8K Views Privacy Terms of Use Policies Contact Us Recommend to library JoVE NEWSLETTERS Research JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive Education JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site Authors Overview Publishing Process Editorial Board Scope and Policies Peer Review FAQ Submit Librarians Overview Testimonials Subscriptions Access Resources Library Advisory Board FAQ ABOUT JoVE Overview Leadership Blog JoVE Help Center Copyright © 2025 MyJoVE Corporation. All rights reserved