Optimization of IEDDA bioorthogonal system: Efficient process to improve trans-cyclooctene/tetrazine interaction

Antibody‐Incorporated Nanomedicines for Cancer Therapy

“…[ 182 ] The efficiency of the iEDDA strategy may be decreased if TCO isomerizes into cis ‐cyclooctene with higher stability but less reactivity. [ 183 ] Besides, the reactive TCO derivatives require storage in cold solutions to avoid isomerization and polymerization. [ 182 ] Although the relatively large reactive groups can lead to faster iEDDA reactions, these reactive groups may have higher possibility of influencing in vivo biological processes.…”

Click Chemistry and Targeted Degradation: A Winning Combination for Medicinal Chemists?

“…[21,22] Three out of the most famous bioorthogonal transformations are (i) the Staudinger ligation [4,23] , (ii) the strain-promoted azide-alkyne cycloaddition (SPAAC), also called as "Cu-free click chemistry" [21,24] and (iii) inverse electron demand Diels-Alder (IEDDA) cycloaddition (Figure 2). [25][26][27] The Staudinger reaction is the first reported bioorthogonal reaction between an azide and a phosphine, resulting in an amide. [4,28] In turn, SPAAC reaction was developed by Bertozzi to eliminate the cytotoxic effect of copper in vivo.…”

“…IEDDA is believed as the fastest bioorthogonal reaction (Figure 2). It is performed between tetrazine and trans‐cyclooctene (TCO) derivatives and, since its description by Blackman, is successfully used for many biomedical applications [25–27,30] …”

“…It is performed between tetrazine and trans-cyclooctene (TCO) derivatives and, since its description by Blackman, is successfully used for many biomedical applications. [25][26][27]30] The simplicity, speed, ease, and wide scope of click/ bioorthogonal chemistry have been so much appreciated that both strategies are widely used in the search of many drugs, e. g., anticancers, antivirals, peptidomimetics, antiparasitics or anti-inflammatories. [31,32] As highlighted by the Nobel Committee, [33] thanks to its modular nature and robustness, the principle may be equated to an "IKEA 'flatpack' approach, in which all necessary components, the 'building blocks', along with a set of easy-touse hardware, the 'reactions', were provided together with a reliable assembly instruction for almost anybody to follow".…”

Tetrazine bioorthogonal chemistry makes nanotechnology a powerful toolbox for biological applications

“…4,13 As such, the IEDDA ligation techniques are quite promising and have been applied in various fields. [14][15][16][17] A robust synthesis of this IEDDA partner was reported by the Fox group in 2008 utilizing a one-step reaction around flow photo isomerization. 17 The broad utilization of this ligation in biological applications should be attributed to its rapid kinetics and high selectivity, which ensure highly efficient and specific modification of their target agents even at complicated in vivo environments even under extraordinarily low reagent concentrations.…”