Sulfo-SE Peptide Labeling Without Autoreactivity
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Solution Overview
Problem
Current methods for labeling biomolecules with sulfo-n-hydroxysuccimidyl ester (sulfo-SE) peptides face challenges due to autoreactivity issues with peptides containing nucleophilic amino acids like arginine, lysine, histidine, cysteine, serine, tyrosine, and glutamic acid, limiting their use in labeling biomolecules effectively.
Innovation Solution
Development of sulfo-SE linked peptides that are stably modified on non-alkyl amino acids such as serine, threonine, tyrosine, glutamic acid, and aspartic acid, avoiding autoreactivity, and used for labeling biomolecules by reacting with primary amines on the biomolecules, with the sulfo-SE group attached to the N-terminus, C-terminus, or side chain of the peptide.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If SE groups are used to label biomolecules, then labeling efficiency is improved, but autoreactivity with nucleophilic amino acids occurs
Solution Approach 1:
The patent extracts the problematic interaction by removing lysine and cysteine residues from the peptide sequence, eliminating the nucleophilic amino acids that cause autoreactivity with the SE group, while preserving other nucleophilic residues (arginine, histidine, serine, tyrosine, aspartic acid, glutamic acid) that do not interfere with SE group stability
Solution Approach 2:
The patent changes the chemical environment parameters by modifying the peptide sequence composition (removing specific amino acids) and controlling pH conditions during synthesis and labeling to prevent unwanted reactions between the SE group and nucleophilic residues
2Adaptability or versatility
If peptides with nucleophilic amino acids are used, then functional versatility is improved, but stability of sulfo-SE modification deteriorates
Solution Approach 1:
The patent applies local quality by selectively removing only the problematic nucleophilic residues (lysine and cysteine) from specific positions in the peptide sequence while preserving other nucleophilic amino acids at positions where they do not interfere with SE group stability, thus maintaining functional versatility in specific regions while ensuring stability where needed
Solution Approach 2:
The patent introduces an intermediary approach by using alternative nucleophilic amino acids (arginine, histidine, serine, tyrosine, aspartic acid, glutamic acid) that can participate in functional interactions without causing unwanted reactions with the SE group, effectively mediating between functional requirements and stability requirements
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
Enables stable and efficient labeling of biomolecules like antibodies and streptavidin without autoreactivity issues, allowing for the use of sulfo-SE peptides as universal reagents for conjugating peptides to targets of interest, enhancing bioluminescent assays and platforms.
Implementation Method 1
The primary amine of lysine amino acids is a widely available reactive moiety on biomolecules and reacts readily with various agents, for example, an n-hydroxy succinimidyl ester (SE) group
Data Source
AI summary
Provided herein are sulfo n-hydroxysuccimidyl ester (sulfo-SE) linked peptides, methods of synthesis thereof, and methods of using such peptides for labeling of biomolecules. In particular, peptides comprising non-alkyl group such as serine, threonine, cysteine, tyrosine, glutamic acid, and aspartic acid are stably modified (e.g., without autoreactivity) with a sulfo-SE group and used to label or otherwise modify biomolecules.