Peptide Tag Composition to Reduce Cytoplasmic Protein Aggregation
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Solution Overview
Problem
Intracellular antibodies and proteins face stability issues due to aggregation in the cytoplasm, leading to reduced expression levels and functional inhibition, with existing peptide tags containing 45% or more acidic amino acids focusing on endosomal pH rather than cytoplasmic pH.
Innovation Solution
A peptide tag with 5% to 45% acidic amino acids and 20% to 70% of F, P, Y, G, S, Q, N, and A amino acids, along with limited M, T, W, C, I, V, and L, reduces aggregation by optimizing for cytoplasmic stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If an antibody is expressed in the cytoplasm, then intracellular antibody function is achieved, but aggregation occurs leading to reduced stability and expression level
Solution Approach 1:
A peptide tag is introduced as an intermediary component between the antibody and the cytoplasmic environment. This peptide tag, with specifically optimized amino acid composition (5-45% acidic amino acids and 20-70% F, P, Y, G, S, Q, N, A), acts as a mediator that prevents aggregation of the antibody in the cytoplasm while allowing the antibody to maintain its intracellular function. The peptide tag absorbs the harmful interaction between the antibody and the cytoplasmic environment.
2Adaptability or versatility
If existing peptide tags with 45% or more acidic amino acids are used, then endosomal pH optimization is achieved, but cytoplasmic aggregation is not sufficiently prevented
Solution Approach 1:
The amino acid composition parameters of the peptide tag are fundamentally changed from the conventional design (≥45% acidic amino acids optimized for endosomal pH) to a new parameter range (5-45% acidic amino acids with 20-70% F, P, Y, G, S, Q, N, A). This parameter change shifts the optimization focus from endosomal pH environment to cytoplasmic stability, thereby preventing aggregation in the cytoplasm while maintaining adequate adaptability.
3Stability of the object's composition
If protein aggregation is reduced, then intracellular stability is improved, but expression level must be maintained
Solution Approach 1:
The peptide tag with optimized amino acid composition provides self-service functionality by automatically preventing aggregation of the fused protein in the cytoplasm. This aggregation prevention mechanism inherently maintains protein stability and expression levels without requiring additional external interventions or complex systems. The peptide tag serves itself to solve the aggregation problem while preserving productivity.
Data Source
AI summary
The present disclosure provides a peptide tag, and a nucleic acid encoding the peptide tag. The peptide tag of the present disclosure can reduce an aggregation property of a protein in a cell. Specifically, the peptide tag of the present disclosure can be a peptide tag in which 5% or more and less than 45% of amino acids contained in an amino acid sequence thereof are acidic amino acids, and (b) 20% or more of the amino acids contained in the amino acid sequence are amino acids selected from the group consisting of F, P, Y, G, S, Q, N, and A.