Solid-Phase Synthesis of NIR Fluorescent Probe
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Solution Overview
Problem
The current synthesis process for the Near-InfraRed (NIR) fluorescent probe DA364, which involves a Cy5.5 dye conjugated with an aza-bicycloalkane based cyclic peptide, is lengthy, requires high yields, and is costly due to its complex procedure with multiple steps and low recovery rates.
Innovation Solution
A solid-phase synthesis method is introduced, where the conjugation of the aza-bicycloalkane cyclic peptide RGD to the Cy5.5 dye is performed directly on a resin, reducing the number of steps, time, and resource consumption, and allowing for automation and increased yield.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If the current solution-phase synthesis method is used for DA364, then the conjugation of Cy5.5 dye to aza-bicycloalkane based cyclic peptide can be achieved, but the synthesis process becomes lengthy with multiple steps and low recovery rates
Solution Approach 1:
The patent changes the physical state parameter of the synthesis system from solution-phase to solid-phase, where the cyclic peptide is anchored to a solid support. This parameter change enables automated repetitive steps (coupling, washing, deprotection) while maintaining conjugation specificity, thereby resolving the contradiction between manufacturing precision and productivity.
2Reliability
If the current multi-step synthesis procedure is followed, then the DA364 probe can be synthesized with proper conjugation, but the number of steps increases and recovery rates decrease
Solution Approach 1:
The patent segments the synthesis process into distinct modular steps (amino acid coupling, cyclization, deprotection, dye conjugation, cleavage) performed on solid support. Each step can be independently optimized and automated, reducing overall procedure complexity while maintaining reliable conjugation quality through controlled conditions at each stage.
Solution Approach 2:
The solid support acts as an intermediary that temporarily holds the cyclic peptide during synthesis. This intermediary enables easy separation of reactants and products at each step, simplifies purification, and maintains high recovery rates while ensuring proper conjugation quality.
3Adaptability or versatility
If solution-phase synthesis is used, then the reaction flexibility is maintained, but the production time increases and costs increase
Solution Approach 1:
The solid support performs self-service functions by automatically facilitating each synthesis step through simple washing and coupling cycles. The resin beads can be easily separated, washed, and reused for multiple coupling cycles, enabling rapid sequential reactions without time-consuming filtration or purification steps between reactions, thus reducing production time while maintaining reaction flexibility.
Data Source
AI summary
The present invention discloses a solid-phase process for the preparation of a Near Infra-Red (NIR) fluorescent probe characterized by an aza-bicycloalkane based cyclic peptide labelled with a Cy5.5 dye moiety and used in the guided surgery of tumors and pathologic regions.