Cyclic Peptides Variable Constant Regions Sequencing
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Solution Overview
Problem
There is a need for improved protein targeting peptides that are readily sequenceable and can be used as affinity agents for detecting disease-related proteins, as existing methods are limited in their ability to identify and utilize cyclic peptides effectively.
Innovation Solution
The development of cyclic peptides with a variable region for target binding and a constant region for aiding in sequencing and screening, which can be synthesized using solid-state techniques and modified with chemical groups for stability and biochemical properties, allowing for efficient identification and use as protein targeting agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If cyclic peptides are used as protein targeting agents, then affinity and selectivity for target proteins are improved, but difficulty in sequencing and identification increases
Solution Approach 1:
The cyclic peptide is segmented into a variable region (for target binding) and a constant region (containing sequencing-friendly amino acids at N- and C-termini). This segmentation allows the peptide to maintain its cyclic structure for high affinity while providing accessible terminal residues for sequential Edman degradation sequencing.
Solution Approach 2:
Different regions of the peptide are assigned different qualities: the variable region contains diverse amino acids for target recognition and binding affinity, while the constant region contains specific amino acids (such as those suitable for Edman degradation) that facilitate sequencing. This local differentiation resolves the contradiction between maintaining cyclic structure for affinity and providing sequencing accessibility.
2Reliability
If large peptide libraries are screened to identify protein binders, then affinity agents are identified, but time and resources required for identification increase
Solution Approach 1:
The peptide libraries are pre-designed with constant regions containing amino acids that are readily sequenceable by Edman degradation. This preliminary structuring eliminates the need for complex alternative sequencing methods after screening, allowing rapid identification and characterization of binders without time-consuming method development.
Solution Approach 2:
The invention changes the compositional parameters of the peptide libraries by incorporating specific amino acids in the constant regions that optimize both binding capability and sequencing efficiency. This parameter optimization allows simultaneous achievement of reliable binder identification and rapid sequencing confirmation.
3Productivity
If cyclic peptides are synthesized using solid-state techniques, then manufacturing efficiency is improved, but structural complexity and purification difficulty increase
Solution Approach 1:
The cyclic peptide is synthesized as segments (variable region and constant region) that can be independently assembled through solid-state techniques. This segmentation simplifies the synthesis process by breaking down the complex cyclic structure into manageable pieces that can be efficiently produced and then cyclized, maintaining high productivity while managing structural complexity.
Data Source
AI summary
Peptides having activity as protein binding agents are disclosed. The peptides have the following structure (I):including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein R, R1, L1, L2, G, M, Y1 Y2 and SEQ are as defined herein. Methods associated with preparation and use of such peptides, as well as pharmaceutical compositions comprising such peptides, are also disclosed.