Click-to-release Reagents: TCO (trans-cyclooctene) Derivatives & many more

trans-Cyclooctene (TCO) derivatives and 1,2,4,5-tetrazine (Tz) derivatives undergo highly selective and rapid reactions via the inverse electron-demand Diels–Alder (IEDDA) reaction. Compared to alkyne-azide click reactions (CuAAC, SPAAC), the IEDDA reaction proceeds faster, requires no metal catalysts, and exhibits excellent bioorthogonality.

Carbamate-modified TCO* (2-TCO) and certain Tz derivatives are known to release amine compounds following the IEDDA reaction, in what is called a "click-to-release" process. This click-to-release strategy has been applied to prodrug development and protein caging systems.

1. Click-to-Release Reagents

2. trans - Cyclooctene (TCO) derivatives and 1,2,4,5-tetrazine ( Tz ) derivatives undergo highly selective and rapid reactions via the inverse electron-demand Diels–Alder (IEDDA) reaction. Compared to alkyne- azide click reactions ( CuAAC , SPAAC), the IEDDA reaction proceeds faster, requires no metal catalysts, and exhibits excellent bioorthogonality . Carbamate-modified TCO* (2-TCO) and certain Tz derivatives are known to release amine compounds following the IEDDA reaction, in what is called a "click-to-release" process. This click-to-release strategy has been applied to prodrug development and protein caging systems. Introduction

3. Scheme of the Click-to-Release

4. This reaction enables the controlled release of molecules at desired times and locations without the use of catalysts, owing to its highly selective and ultrafast click reactivity under physiological conditions. Importantly, this is a clean reaction, producing only N 2  and CO 2  as byproducts . For preparation of TCO*-payloads, the axial isomer of TCO* is preferable. It has been reported that the axial isomer reacts via IEDDA approximately 150 times faster than the equatorial isomer . In the release process following the IEDDA reaction, the substituents on the tetrazine ( Tz ) play a critical role. Among tetrazine derivatives, Me- Tz (3-methyl-1,2,4,5-tetrazine) is widely used. While H- Tz (1,2,4,5-tetrazine) undergoes IEDDA faster than Me- Tz , it is known to exhibit significantly reduced release efficiency afterward.

5. Advantages High-purity isomers of TCO* (axial and equatorial) are individually isolated and in our product lineup. TCO*-payloads can be synthesized from the  p - nitrophenylcarbonate ester of TCO* axial isomer (Product No. T4218 ) Various Me- Tz derivatives are available as our products, allowing you to select the most suitable reagent for your experiments.

6. Products TCO* Derivative

7. Me- Tz Derivatives

8. for Carboxy Groups

9. for Azido Groups

10. for Alkynes for Avidins

11. for Others

12. Product Number Product Name T4218 TCO*-NPC axial isomer T4219 TCO*-NPC equatorial isomer M3494 Methyltetrazine-NHS Ester D6331 Methyltetrazine-amido-PEG3-NHS Ester M3468 Methyltetrazine-PEG4-NHS Ester M3558 [4-(6-Methyl-1,2,4,5-tetrazin-3-yl)phenyl]methanamine Hydrochloride A3721 Methyltetrazine-amido-PEG3-Amine Hydrochloride M3767 Methyltetrazine-amido-PEG3-Alkyne M3769 Methyltetrazine-amido-PEG3-DBCO A3697 Methyltetrazine-amido-PEG3-Azide M3768 Methyltetrazine-amido-PEG3-Biotin M3469 [4-(6-Methyl-1,2,4,5-tetrazin-3-yl]phenyl)methanol B6382 3-[4-( Bromomethyl )phenyl]-6-methyl-1,2,4,5-tetrazine

13. PLEASE CONTACT TCI FOR MORE INFORMATION www.TCIchemicals.com/IN/en | [email protected]