Bi-functionalized Trans-cyclooctenes for Rapid Click Release
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Solution Overview
Problem
Current trans-cyclooctenes do not meet the criteria for enhanced clinical capability, requiring bi-functionalization with multiple handles for fast click reactions and rapid release of a releasable moiety, which is not synthetically accessible or efficient.
Innovation Solution
Development of bi-functionalized trans-cyclooctenes with specific functional groups that allow for rapid click reactions and release kinetics, including compounds of formula (I) with moieties X1 and X2, Y, and a conjugate formation with pharmaceutically active substances or targeting moieties, enabling efficient release upon contact with a 1,2,4,5-tetrazine.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If trans-cyclooctenes are functionalized with multiple handles for fast click reactions, then the click reaction speed is improved, but the synthetic accessibility and ease of manufacture deteriorate
Solution Approach 1:
The trans-cyclooctene molecule is segmented into distinct functional regions: a core TCO unit and separate functional handles (e.g., ester groups, halogens) that can be independently optimized. This allows the click reaction site to be enhanced for speed while the synthetic accessibility is maintained through modular assembly of functional components.
Solution Approach 2:
The patent modifies chemical parameters of the trans-cyclooctene structure by introducing specific functional groups (ester moieties, halogen substituents) at defined positions. These parameter changes enable fast click reaction kinetics while maintaining synthetic accessibility through established chemical transformations.
2Speed
If trans-cyclooctenes are designed to release releasable moieties rapidly after click, then the release kinetics are improved, but the device complexity and structural complexity increase
Solution Approach 1:
The patent employs an intermediary ester group as a linker between the trans-cyclooctene core and the releasable moiety. This intermediary structure enables rapid release kinetics through ester hydrolysis or cleavage while maintaining relatively simple overall molecular architecture, avoiding excessive structural complexity.
Solution Approach 2:
The design incorporates a releasable moiety that can be discarded or released after serving its function in the conjugate. The ester-linked moiety can be cleaved and released rapidly after the click reaction, enabling fast release kinetics without requiring complex structural systems for moity recovery or recycling.
3Ease of manufacture
If bi-functionalized trans-cyclooctenes are synthesized via straightforward routes, then the ease of manufacture is improved, but the ability to meet multiple clinical criteria (fast click, release, stability) deteriorates
Solution Approach 1:
The patent designs trans-cyclooctene derivatives with multi-functional capabilities: the core structure provides click reactivity, while attached functional groups (ester, halogen, carbonyl) provide additional handles for conjugation and release functions. This multi-functionality allows a single compound to meet multiple clinical criteria including fast click reaction, controlled release, and stability, while maintaining synthetic accessibility through systematic assembly of functional modules.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The bi-functionalized trans-cyclooctenes facilitate rapid and efficient release of pharmaceutically active substances or targeting moieties upon click reaction, enhancing their clinical utility and therapeutic potential.
Implementation Method 1
the in vivo click reaction between radiolabelled tetrazines and trans-cyclooctene (TCO) functionalized with an antibody has been shown for this purpose
Data Source
AI summary
The present invention relates to novel bi-functionalized trans-cyclooctenes of formula (1). It also relates to conjugates, compositions, medical uses of such compounds, and methods for producing such compounds as well as conjugates of such compounds.