SPAAC Click Reaction

Strain-promoted azide-alkyne cycloaddition (SPAAC) click reaction was popularized in 2004 by Bertozzi, a famous organic chemist and molecular cell biologist in the United States. This reaction occurs between an azide and a cycloalkyne by ring strain rather than copper catalysts to form a stable triazole. The schematic diagram of the SPAAC click reaction is shown in scheme 1.

Scheme 1. Schematic diagram of the SPAAC click reaction.

Advantages

SPAAC click reaction does not require metal catalysts, reducing agents, or stable ligands. Instead, it only relies on the enthalpy released from the ring strain of cyclooctyne to form a stable triazole. Thus, SPAAC click reaction has many advantages, including but not limited to the following.

• High yield: SPAAC click reaction has no by-products, so the yield is very high.
• Low toxicity: SPAAC click reaction does not involve metal catalysts that may cause biotoxicity by releasing metal ions, so the reaction is low toxicity.
• High selectivity: SPAAC click reaction is inert to acids, oxides, and active amino acid molecules, so it has high selectivity.
• Others: Other advantages of SPAAC click reaction include mild reaction conditions, high reaction rate, and good biorthogonality.

Applications

SPAAC click reaction has been extensively used in many fields such as polymer chemistry and medicine. The details are as follows.

• In polymer chemistry

In recent years, SPAAC click reaction has gained widely attention in polymer chemistry. It has been shown that SPAAC click reaction can be used to modify 2D and 3D polymer frameworks in the absence of catalysts and other added reagents. In addition, it is also used for the preparation of precision polymers, and polymer grafted nanostructures (e.g. enzymes, antibodies and cell-surface receptors). SPAAC click reaction offers a new approach to polymer discovery.

• In medicine

SPAAC click reaction is a simple conjugation strategy for linking different functional elements to prostate-specific membrane antigen (PSMA) ligands. Derks et al^[1]. synthesized and characterized four dual-labeled PSMA ligands for intraoperative radio-detection and fluorescence imaging of prostate cancer. The results demonstrated that the PSMA ligands synthesized by SPAAC click reaction had high PSMA specific tumor targeting. The application of SPAAC click reaction in the development of PSMA ligands offers the possibility of fast, efficient, and versatile conjugations of multiple imaging moieties or drugs.

What Can We Do?

As a leading customer-focused company, Alfa Chemistry has experienced experts and professional R & D laboratories. For many years, we have been focusing on reagent development and potential application exploration of the SPAAC click reaction. If you have questions about the SPAAC click reaction, please contact us. We will draw upon our wide range of advantages and high-quality products to create customized, scalable, efficient solutions for your research.

Reference

1. Derks, Y.H.W.; et al. Strain-promoted azide-alkyne cycloaddition-based PMSA-targeting ligands for multimodal intraoperative tumor detection of prostate cancer. Bioconjugate Chemistry. 2022, 33: 194-205.