Modified GC-C Receptor Agonist Peptide Synthesis With Controlled Cyclization
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Solution Overview
Problem
There is a need for more effective and well-tolerated treatments for interstitial cystitis/bladder pain syndrome (IC/BPS), particularly due to the inefficacy of current therapies and the lack of diagnostic tests, and a requirement for an efficient synthesis and purification process for a 13-amino-acid guanylate cyclase C (GC-C) agonist synthetic peptide for treating bladder pain.
Innovation Solution
A method is developed for synthesizing a synthetic peptide with a specific amino acid sequence (Cys1 Cth2 Glu3 Leu4 Cys5 Cys6 Asn7 Val8 Ala9 Cys10 Tyr11 Gly12 Cys13) involving chemical synthesis, cyclization, and purification, including steps like binding to a solid phase support, cleavage, coupling, deprotection, folding, and optional N-terminus modification, to produce a peptide with covalent bonds between specific amino acid residues.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional peptide synthesis methods are used, then the basic peptide structure can be produced, but the synthesis efficiency is low and purification is cumbersome
Solution Approach 1:
The peptide synthesis is divided into distinct modular steps: solid phase synthesis of the backbone, selective deprotection of specific amine groups, intramolecular cyclization to form disulfide bonds, and final purification. This segmentation allows each step to be optimized independently, improving overall efficiency while maintaining control over the complex process.
Solution Approach 2:
Protecting groups are strategically installed on specific amine groups during the synthesis phase before cyclization. This preliminary action enables selective deprotection and subsequent intramolecular cyclization to form the correct disulfide bond configuration, ensuring high purity product without requiring complex purification procedures.
2Manufacturing precision
If multiple protecting groups are used to control cyclization, then the correct peptide structure can be formed, but the synthesis steps increase
Solution Approach 1:
Different protecting groups are applied to different amine groups in the peptide sequence based on their specific requirements. This local differentiation allows precise control over which amine groups participate in cyclization and which remain free, ensuring accurate peptide structure formation with manageable synthesis steps.
Solution Approach 2:
Protecting groups serve as intermediary elements that temporarily block specific amine groups during synthesis, then are selectively removed to enable controlled cyclization. This intermediary mechanism provides precise structural control while maintaining a relatively streamlined synthesis process by avoiding the need for multiple separate protection/deprotection cycles.
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 enables the production of a synthetic peptide that can be used effectively for treating IC/BPS, offering a potential treatment for bladder pain and other visceral pain conditions, with improved synthesis and purification processes ensuring quality and efficacy.
Implementation Method 1
chemically synthesizing a linear peptide having its C-terminus bound to a solid phase support
Implementation Method 2
cleaving the linear peptide from the solid phase support to generate a protected peptide
Implementation Method 3
coupling an amino acid to the C-terminus of the protected peptide
Implementation Method 4
removing one amine protecting group and one carboxylic acid protecting group of the protected peptide
Implementation Method 5
coupling the unprotected amine and the unprotected carboxylic acid group to form a cyclized peptide
Implementation Method 6
folding the globally deprotected peptide to form one or more additional crosslinks to obtain the synthetic peptide
Data Source
AI summary
The present invention relates to methods of producing a synthetic peptide or pharmaceutically acceptable salts thereof of SEQ ID NO: 1.