Biomaterial Database

Optimization of IEDDA bioorthogonal system: Efficient process to improve trans-cyclooctene/tetrazine interaction. 2020

Jean-Baptiste Béquignat, and Nancy Ty, and Aurélie Rondon, and Ludivine Taiariol, and Françoise Degoul, and Damien Canitrot, and Mercedes Quintana, and Isabelle Navarro-Teulon, and Elisabeth Miot-Noirault, and Claude Boucheix, and Jean-Michel Chezal, and Emmanuel Moreau

Université Clermont Auvergne, Imagerie Moléculaire et Stratégies Théranostiques, BP 184, F-63005, Clermont-Ferrand, France; Inserm, U 1240, F-63000, Clermont-Ferrand, France; Centre Jean Perrin, F-63011, Clermont-Ferrand, France.

The antibody pretargeting approach for radioimmunotherapy (RIT) using inverse electron demand Diels-Alder cycloaddition (IEDDA) constitutes an emerging theranostic approach for solid cancers. However, IEDDA pretargeting has not reached clinical trial. The major limitation of the IEDDA strategy depends largely on trans-cyclooctene (TCO) stability. Indeed, TCO may isomerize into the more stable but unreactive cis-cyclooctene (CCO), leading to a drastic decrease of IEDDA efficiency. We have thus developed both efficient and reproducible synthetic pathways and analytical follow up for (PEGylated) TCO derivatives, providing high TCO isomeric purity for antibody modification. We have set up an original process to limit the isomerization of TCO to CCO before the mAbs' functionalization to allow high TCO/tetrazine cycloaddition.

UI	MeSH Term	Description	Entries
D007536	Isomerism	The phenomenon whereby certain chemical compounds have structures that are different although the compounds possess the same elemental composition. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)	Isomerisms
D011092	Polyethylene Glycols	Polymers of ETHYLENE OXIDE and water, and their ethers. They vary in consistency from liquid to solid depending on the molecular weight indicated by a number following the name. They are used as SURFACTANTS, dispersing agents, solvents, ointment and suppository bases, vehicles, and tablet excipients. Some specific groups are NONOXYNOLS, OCTOXYNOLS, and POLOXAMERS.	Macrogols,Polyoxyethylenes,Carbowax,Macrogol,Polyethylene Glycol,Polyethylene Oxide,Polyethyleneoxide,Polyglycol,Glycol, Polyethylene,Glycols, Polyethylene,Oxide, Polyethylene,Oxides, Polyethylene,Polyethylene Oxides,Polyethyleneoxides,Polyglycols,Polyoxyethylene
D006573	Heterocyclic Compounds, 1-Ring	Organic compounds that contain a ring structure made up of carbon and one or more additional elements such as nitrogen and oxygen.	Heterocyclic Cpds, 1-Ring,1-Ring Heterocyclic Compounds,1-Ring Heterocyclic Cpds,Heterocyclic Compounds, 1 Ring,Heterocyclic Cpds, 1 Ring
D061565	Cycloaddition Reaction	Synthetic organic reactions that use reactions between unsaturated molecules to form cyclical products.	Cycloaddition,Cycloaddition Reaction Techniques,Diels-Alder Reaction,Cycloaddition Reaction Technique,Cycloaddition Reactions,Diels Alder Reaction,Reaction Technique, Cycloaddition,Reaction Techniques, Cycloaddition,Reaction, Cycloaddition,Reaction, Diels-Alder,Reactions, Cycloaddition,Technique, Cycloaddition Reaction,Techniques, Cycloaddition Reaction
D034242	Cyclooctanes	A group of compounds with an 8-carbon ring. They may be saturated or unsaturated.	Benzocyclooctanes,Benzocyclooctenes,Cyclooctenes,Cyclooctodienes,Dibenzocyclooctanes