Amino Diacid Linkers for Streamlined Peptide Modification
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Solution Overview
Problem
Native peptides and their analogues have high clearance rates, which limits their prolonged biological activity, and modifying peptide chains post-synthetically is complex and challenging, especially when introducing diacid derivatives as linkers.
Innovation Solution
The introduction of novel peptide modifiers, represented by compounds of Formula 1 and their derivatives, allows for selective modification of peptide chains during synthesis, using amino diacids as linkers to enhance water solubility and reduce byproducts.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If post-synthetic modification of peptide chains is performed to reduce clearance rates and enhance biological activity, then the biological activity and duration of action are improved, but the process complexity and difficulty of manufacture increase significantly
Solution Approach 1:
The patent incorporates diacid derivatives as linkers directly into the peptide chain during the synthesis process, rather than performing modifications after synthesis. This preliminary incorporation simplifies the overall process while achieving the desired reduction in clearance rate and enhancement of biological activity duration
Solution Approach 2:
The diacid derivative acts as an intermediary linker molecule that connects to the peptide chain during synthesis. This intermediary approach allows for controlled incorporation of functional groups that reduce clearance without requiring complex post-synthetic modification steps
2Quantity of substance
If diacid derivatives are introduced as linkers to improve water solubility, then the solubility and stability are enhanced, but the synthesis complexity and number of steps increase
Solution Approach 1:
The patent combines the linker function and the solubility-enhancing diacid derivative into a single integrated molecular structure that is incorporated during peptide synthesis. This merging eliminates the need for separate steps to add solubility-enhancing groups, simplifying the overall synthesis process while achieving improved water solubility
3Manufacturing precision
If selective deprotection of amino acid side chains is performed to introduce modifiers, then the specificity of modification is improved, but the number of synthesis steps and time required increase
Solution Approach 1:
The diacid derivative linker is pre-incorporated into the peptide chain during synthesis with the appropriate specificity, eliminating the need for subsequent selective deprotection and modification steps. This preliminary action maintains manufacturing precision while significantly reducing the time required
Data Source
AI summary
The present invention relates to peptide modifier compounds of Formula (1), or a salt thereof, wherein: a is an integer from 1 to 10, more preferably from 1 to 3; b is an integer from 0 to 7; Z is a terminal group and Y is a bivalent group. Further aspects of the invention relate to intermediates in the preparation of compounds of Formula (1), and the use of compounds of Formula (1) in the synthesis of peptide derivatives.