Two-Part RP-Tag Affinity Purification for Recombinant Proteins

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Solution Overview

Problem

Existing methods for identifying, expressing, and isolating recombinant proteins are inefficient, requiring multiple techniques and increasing costs and time, with a need for improved compositions and systems for protein expression, isolation, and identification.

Innovation Solution

A two-part peptide tag system derived from bacterial ribose binding protein, specifically RP-Tag Large and RP-Tag Small, with high affinity and stability, allowing for affinity purification and protein identification, and enhanced solubility and expression of recombinant proteins.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If multiple purification techniques are used to isolate recombinant proteins, then purification reliability is improved, but process complexity and time increase

Engineering Contradiction:
Improvepurification reliabilityVSAvoidprocess complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The ribose binding protein is divided into two separate functional fragments: RP-Tag Large (amino acids 1-136) and RP-Tag Small (amino acids 137-276). This segmentation allows each fragment to serve a specific purpose - RP-Tag Large provides stable binding to the target protein while RP-Tag Small enables high-affinity purification through immobilization on solid supports, eliminating the need for multiple purification techniques

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The two-part RP-Tag system acts as an intermediary between the target recombinant protein and the purification system. RP-Tag Large fused to the target protein mediates specific binding, while RP-Tag Small immobilized on solid support mediates purification capture, simplifying the overall purification process into a single-step affinity chromatography

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If multiple purification techniques are used to isolate recombinant proteins, then purification reliability is improved, but time consumption increases

Engineering Contradiction:
Improvepurification reliabilityVSAvoidtime consumption
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The invention merges the functions of target protein recognition and purification capture into a single two-part tag system. RP-Tag Large provides specific recognition of the target protein while RP-Tag Small provides the purification handle, combining multiple functions into one integrated system that operates in a single purification step

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The RP-Tag fragments are pre-engineered and characterized to ensure optimal binding affinity and purification performance. RP-Tag Large is designed with high stability and specific binding capacity, while RP-Tag Small is optimized for immobilization and capture efficiency, allowing the purification process to proceed rapidly without requiring multiple sequential steps

Inventive Principle:
Principle #10Preliminary action

3Ease of manufacture

If existing purification reagents are used, then current methods are maintained, but cost and time efficiency deteriorate

Engineering Contradiction:
Improvemethod simplicityVSAvoidpurification time
Core Design Contradiction:
Ease of manufactureVSLoss of time

Solution Approach 1:

The two-part RP-Tag system is universally applicable to any recombinant protein of interest. RP-Tag Large can be fused to the N- or C-terminus of any target protein, and RP-Tag Small can be immobilized on various solid supports, creating a universal purification platform that simplifies the purification process across different protein targets

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

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

The RP-Tag system provides robust and stable protein-protein interactions under various conditions, enabling efficient protein isolation and purification, with high affinity and resistance to denaturants, and is suitable for diverse cell systems.

Implementation Method 1

the first protein and second protein have an equilibrium binding constant, Kd, of less than 100 nM

Methodology Applied
Scientific EffectProtein-protein binding interaction:

Data Source

PatentEP3592763B1Compositions, methods, and systems for affinity-based protein identification and purification
Publication Date: 2026.02.25 AUCTUS BIOLOGICS INC
  • EP3592763B1 patent drawingFigure 1~2
  • EP3592763B1 patent drawingFigure 3~4
  • EP3592763B1 patent drawingFigure 5~6

AI summary

Disclosed herein are compositions, methods, and systems for the purification and/or detection of recombinant and other proteins. In some embodiments, compositions may comprise recombinant protein with one or more sequences having substantial homology to RP-Tag Small or RP-Tag Large. In some cases, the disclosed compositions may be useful in binding or recognizing target proteins.