Cyclic Peptide Library Construction via Expression Vectors

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Solution Overview

Problem

Current methods for constructing virtual peptide libraries are limited by high costs and low production yields, making it impractical to synthesize large numbers of peptides, especially for complete libraries like tetrapeptide, pentapeptide, and hexapeptide libraries, which require millions of distinct peptides.

Innovation Solution

The method involves designing cyclic peptides that can display arrays of short peptides, significantly reducing the number of peptides needed by cyclizing linear peptides and using expression vectors for efficient synthesis and purification, allowing a single cyclic peptide to display multiple distinct peptides, thereby increasing library capacity and reducing construction costs.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If conventional chemical synthesis methods are used to construct peptide libraries, then complete libraries can be synthesized, but the cost is extremely high and production yield is low

Engineering Contradiction:
Improvenumber of peptides in libraryVSAvoidmanufacturing cost and complexity
Core Design Contradiction:
Quantity of substanceVSEase of manufacture

Solution Approach 1:

The patent uses a single cyclic peptide sequence that can display multiple different peptides through conformational changes. Instead of synthesizing millions of different peptide sequences, the invention creates one master cyclic peptide template that can present various peptide epitopes, effectively copying the function of multiple peptides from a single source.

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The cyclic peptide structure serves multiple functions simultaneously: it maintains structural stability, presents multiple different peptide epitopes, and can be synthesized once and reproduced indefinitely. This multi-functional design eliminates the need for separate synthesis of each peptide variant in the library.

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Adaptability or versatility

If conventional chemical synthesis is used, then peptide libraries can be constructed, but the time and resources required are prohibitively large

Engineering Contradiction:
Improvelibrary capacityVSAvoidconstruction time
Core Design Contradiction:
Adaptability or versatilityVSLoss of time

Solution Approach 1:

The invention performs preliminary action by synthesizing the cyclic peptide structure once with all necessary amino acid residues in place. The peptide library functionality is pre-established in the cyclic structure, allowing multiple different peptide sequences to be accessed without repeated synthesis steps.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The single cyclic peptide serves as a master template that can generate multiple peptide variants through different conformational states or selective binding, eliminating the need to physically synthesize and store millions of different peptide sequences.

Inventive Principle:
Principle #26Copying

3Quantity of substance

If a complete peptide library is synthesized, then all possible peptide combinations are available, but the number of peptides required is millions making it impractical

Engineering Contradiction:
Improvecompleteness of libraryVSAvoidlibrary construction complexity
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The invention creates a single cyclic peptide template that can display multiple different peptide epitopes. This master template replaces the need to physically construct and manage millions of different peptide molecules, dramatically simplifying the library construction while maintaining completeness.

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The cyclic peptide structure is designed with specific amino acid arrangements that allow it to segment into different functional epitopes. The single cyclic structure contains within it the capability to present multiple distinct peptide sequences through its conformational flexibility or selective binding properties.

Inventive Principle:
Principle #1Segmentation

Data Source

PatentUS11978533B2Peptide library constructing method
Publication Date: 2024.05.07 HUNAN ZONSEN PEPLIB BIOTECH CO LTD
  • US11978533B2 patent drawing
  • US11978533B2 patent drawing
  • US11978533B2 patent drawing

AI summary

An improved peptide library preparation method is described for constructing complete virtual peptide libraries such as a complete virtual tripeptide library, tetrapeptide library, pentapeptide library, hexapeptide library, heptapeptide library, or a complete octapeptide library, etc. The method includes constructing an expression vector for the expression of cyclic peptides. Each cyclic peptide displays an array of peptides of different sizes and sequences, and the number of cyclic peptides needed for constructing a complete virtual peptide library can be dramatically reduced compared with conventional chemical peptide synthesis. Furthermore, the cyclic peptide libraries can be readily reproduced by the expression and purification of the cyclic peptides using the constructed gene libraries. The improved peptide library preparation method can particularly be used, for example, to construct a complete virtual tetrapeptide library, a complete virtual pentapeptide library, a complete virtual hexapeptide library, a complete virtual heptapeptide library, and so on. The improved peptide library preparation method can also be used, for example, to construct a partial pentapeptide library, a partial hexapeptide library, a partial heptapeptide library, and so on. Other related methods and the related expression vectors are also described.