Polymeric Solid Support for Peptide Acid Synthesis
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Solution Overview
Problem
Current solid supports for Fmoc-SPPS of peptide acids are cumbersome and expensive to produce, often result in low yield and purity, and are prone to racemization.
Innovation Solution
A new solid support comprising a compound with a specific polymeric structure, covalently conjugated to a linker, which is synthesized through a three-step reaction scheme, allowing for high-yield and high-purity peptide synthesis with minimal racemization.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If commonly utilized resins (Wang, Atherton, CTC) are used for peptide acid synthesis, then Fmoc-SPPS can be performed, but the preparation is cumbersome and expensive
Solution Approach 1:
The patent applies preliminary action by pre-installing a hydroxyl group on the solid support before coupling the linker. This preliminary functionalization simplifies the overall preparation process, as the hydroxyl group is readily available and facilitates direct coupling with the linker molecule, eliminating the need for complex in-situ generation of reactive groups during resin preparation
Solution Approach 2:
The patent changes the chemical parameters of the solid support by selecting materials with inherent hydroxyl groups (such as crosslinked poly(4-hydroxymethylphenol) or poly(ethylene glycol) with terminal hydroxyls). This parameter change in the solid support's functional groups simplifies the preparation chemistry and reduces the number of synthesis steps required compared to traditional resins
2Productivity
If commonly utilized resins are used for peptide acid synthesis, then synthesis can proceed, but yield and purity are insufficient
Solution Approach 1:
The patent changes key chemical parameters including the solid support's functional group (hydroxyl), the linker structure (carboxylic acid-containing), and the coupling conditions to optimize both yield and purity. These parameter changes create a more efficient coupling reaction that minimizes side reactions and maximizes peptide incorporation efficiency
Solution Approach 2:
The patent employs a composite material system consisting of a polymeric solid support coupled with a specifically designed linker molecule. This composite structure combines the advantages of the polymer matrix with the reactive carboxylic acid group of the linker, creating a synergistic system that enhances both yield and purity of peptide synthesis
3Reliability
If commonly utilized resins are used for peptide acid synthesis, then synthesis can proceed, but racemization occurs
Solution Approach 1:
The patent changes the chemical environment parameters by selecting a solid support and linker combination that maintains physiological pH conditions during coupling. This parameter control prevents the formation of racemization-prone intermediates and maintains the stereochemical integrity of the amino acid residues throughout the synthesis process
Data Source
AI summary
The present invention provides a solid support for Fmoc-solid phase synthesis of peptides. In particular, the solid supports of the invention may be utilized to produce peptide acids.