CCK Receptor Peptide Synthesis Without Chromatographic Purification
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Solution Overview
Problem
Existing methods for synthesizing peptides with cholecystokinin (CCK) receptor agonist/antagonist activity are limited by low yield and unsuitable for preclinical CMC-stage production, requiring improvements in scalability and purity.
Innovation Solution
A solution-phase method for preparing peptides with cholecystokinin (CCK) receptor agonistic and/or antagonistic activity, involving stepwise peptide coupling reactions and protecting group manipulations, eliminating the need for chromatographic purification and enabling scalable and reproducible manufacturing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If solid-phase synthesis is used for peptide preparation, then activity screening can be performed, but the yield is low and it is not suitable for preclinical CMC-stage production
Solution Approach 1:
The patent transitions from solid-phase synthesis to solution-phase synthesis, fundamentally changing the reaction medium parameter. This enables scalable manufacturing while maintaining peptide quality, as solution-phase methods allow for larger reaction volumes and easier process optimization for preclinical CMC-stage production
Solution Approach 2:
The patent replaces the mechanical filtration and column chromatography steps inherent in solid-phase synthesis with solution-phase chemistry that uses precipitation and extraction methods. This substitution eliminates equipment-intensive purification steps and enables more scalable production processes suitable for industrial manufacturing
2Manufacturing precision
If column chromatography or HPLC purification is used, then high purity compounds can be obtained, but the process complexity and cost increase
Solution Approach 1:
The patent extracts the peptide product from the reaction mixture through selective precipitation and extraction steps, obtaining high-purity compound without requiring column chromatography or HPLC. This extraction-based purification maintains manufacturing precision while dramatically reducing device complexity and process steps
Solution Approach 2:
The patent employs simple, disposable purification steps such as precipitation and extraction that do not require expensive, complex chromatography systems. These simpler methods achieve comparable purity for preclinical materials while reducing equipment investment and operational complexity
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 method achieves high chemical yield and optical purity, ensuring high chemical yield and optical purity, and compatibility with preclinical CMC needs, producing pharmaceutical-grade compounds.
Implementation Method 1
Condensation of compound 03 with compound 04 to yield compound 05; Condensation of compound 06 with compound 07 to yield compound 08; Condensation of compound 09 with compound 10 to obtain compound 11
Implementation Method 2
Deprotection of the amino protecting group of compound 05 to obtain compound 06; Deprotection of the amino protecting group of compound 08 to obtain compound 09; Removal of the carboxyl protecting group of compound 11 to yield compound 12
Data Source
AI summary
The present invention discloses a method for preparing a peptide compound with CCK receptor agonistic and/or antagonistic activity. The method uses a sequence of solution-phase reactions to generate high-purity and scalable product without chromatographic purification, suitable for industrial production and pharmaceutical development.