Cyclooctynes for Click Chemistry

Technology

Using an integrated computational and experimental process, the inventors have developed a novel class of SPAAC reagents that has both increased bond strain, and increased transition state stability. Compared to current state of the art SPAAC reagents, this technology has significantly improved reaction kinetics, without compromising stability. Additionally, the reagents can be synthesized in a simple, three-step synthesis, making it a promising novel class of reagents for pharmaceutical, biological research, and materials chemistry applications.  

Problem Addressed

This technology accelerates the rate of SPAACs and other 1,3-dipolar cycloaddition reactions. Two approaches have been used to improve SPAAC reagent reaction kinetics without compromising selectivity and stability: increasing bond strain (pre-distortion) and fine-tuning transition state stabilization, however, prior to this invention, attempts suffered from tradeoffs, and multistep syntheses. This three-step synthesis produces a novel class of stable, highly selective, fast-reacting cyclooctynes useful for click chemistry applicable to the fields of chemical biology, polymer chemistry, and materials chemistry.  

Advantages

• Allows for alternative reagents to be used in the 1,3-dipolar cycloaddition reaction with a faster rate of reaction than any other options commercially available for cycloadditions.  

• Provides a systematic process for the generation of stable, efficient, and highly selective click chemistry reagents.  

• High selectivity - azides and alkynes rarely react with other cellular components so SPAAC can occur inside complex biological systems.  

• Biocompatibility - the cycloaddition reaction conditions do not harm living cells or organisms.  

• Fast reaction kinetics - using strained alkynes gives fast reaction rates at low concentrations needed for living systems.  

• Offers a wide variety of applications, such as in drug discovery, novel peptide therapeutic development, radioactive imaging, and polymeric materials augmentation.