Strained Alkenes for IEDDA

Pfizer compound category

A well-known bioorthogonal reaction is the Inverse Electron Demand Diels–Alder (IEDDA) cycloaddition between strained alkenes (such as norbornenes, trans-cyclooctenes, and cyclopropenes) and 1,2,4,5-tetrazines (electron-deficient dienes). This reaction is exceptionally fast, does not require a catalyst, and proceeds cleanly in complex biological systems without perturbing the biological milieu. The two major applications of strained alkene–tetrazine cycloadditions include: bioconjugation (for example, linking small molecules to antibodies or proteins) and click-to-release chemistry (enabling the controlled release of a functional payload upon reaction between tetrazine and trans-cyclooctene).