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Updated: Jul 15, 2025

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions

Published on: December 1, 2020

Split-Protein Therapeutic Platforms: Identifying Binder Pairs.

Christine S Nervig¹, James R Gustat², Shawn C Owen^3,4,5

¹Department of Medicinal Chemistry, University of Utah, Salt Lake City, UT, USA.

Methods in Molecular Biology (Clifton, N.J.)

|September 29, 2023

Summary

This summary is machine-generated.

Researchers developed methods to create safer therapeutic proteins. By splitting proteins and using antibody binders, they enable conditional activation, reducing off-target effects for improved disease treatment.

Keywords:

Antibody Complementation Computational modeling Conditionally active Protein engineering Protein switch Split-enzyme

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Published on: April 20, 2018

Area of Science:

Biotechnology
Protein Engineering
Immunotherapy

Background:

Therapeutic proteins offer advanced treatment options for diseases resistant to small molecule drugs.
Off-target or systemic activity poses a significant challenge in protein-based therapies.
Conditional activation strategies are crucial for enhancing the safety and efficacy of protein therapeutics.

Purpose of the Study:

To describe methods for identifying antibody pairs that facilitate the reconstitution of active therapeutic proteins.
To provide computational and empirical approaches for developing conditionally active protein constructs.
To enable the design of targeted protein therapies using only protein sequence data.

Main Methods:

Splitting therapeutic proteins into inactive fragments.
Fusing protein fragments to binders targeting distinct cell surface epitopes.
Utilizing computational and empirical strategies to identify functional antibody pairs.
Assessing antibody-mediated proximity-induced protein reconstitution.

Main Results:

Demonstrated approaches to determine suitable antibody pairs for protein reconstitution.
Provided general methods applicable to various therapeutic proteins.
Facilitated the identification of antibody pairs starting from protein sequence data.

Conclusions:

Conditionally active protein constructs can mitigate toxicity associated with therapeutic proteins.
Antibody-mediated targeting and reconstitution offer a promising strategy for localized protein activation.
The described methods support the development of safer and more effective protein-based medicines.