Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Protein-protein Interfaces

Protein-protein Interfaces

Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

Inhibitors of the Machupo Virus L Endonuclease for Bolivian Hemorrhagic Fever Treatments.

Microorganisms·2026

Same author

Covalent tumor anchoring spatially orchestrates antitumor immunity.

bioRxiv : the preprint server for biology·2026

Same author

Imaging of <i>Staphylococcus aureus</i> infections and biofilms using a selective covalent probe for the unique serine hydrolase FphE.

bioRxiv : the preprint server for biology·2026

Same author

Epigenetic age acceleration measures and chemotoxicity in older adults with early breast cancer.

GeroScience·2026

Same author

Imaging of Staphylococcus aureus Infections and Biofilms Using a Selective Covalent Probe for the Unique Serine Hydrolase FphE.

Angewandte Chemie (International ed. in English)·2026

Same author

A broad cathepsin inhibitor blocks crystal-stimulated inflammasome-dependent and -independent inflammation and gout arthritis.

Communications medicine·2026

Same journal

Switching Site Selectivity in Alkoxyamine Hydration: From Lone-Pair Direction to Solvent Network Dominance.

Journal of the American Chemical Society·2026

Same journal

A Topotactic Leap: 2D Layers to 3D Large-Pore Zeolite.

Journal of the American Chemical Society·2026

Same journal

Enhanced Hydrogen Evolution over Single-Atom Catalysts via Electrostatic Polarization in Contact-electro-catalysis.

Journal of the American Chemical Society·2026

Same journal

Tumor Acidity-Activatable Ionizable Lipid Nanoparticles for Selective Oncolytic Therapy.

Journal of the American Chemical Society·2026

Same journal

Alternating Magnetic Field Promotes Ammonia Cracking by Disrupting the Sabatier Limitation of Ruthenium Catalytic Species.

Journal of the American Chemical Society·2026

Same journal

Bulk Ferromagnetic Icosahedral Quasicrystals without Rapid Quenching.

Journal of the American Chemical Society·2026

See all related articles

Search research articles

Related Experiment Video

Updated: Jun 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

Identification of Covalent Cyclic Peptide Inhibitors Targeting Protein-Protein Interactions Using Phage Display.

Sijie Wang¹, Franco F Faucher², Matilde Bertolini³

¹Department of Pathology, School of Medicine, Stanford University, Stanford, California 94305, United States.

Journal of the American Chemical Society

|February 24, 2025

Summary

This summary is machine-generated.

Researchers developed a new method to discover covalent macrocyclic drugs that target protein-protein interactions. This approach identified irreversible antiviral compounds against SARS-CoV-2, highlighting potential for long-lasting therapeutic effects.

More Related Videos

A Protocol for Phage Display and Affinity Selection Using Recombinant Protein Baits

A Protocol for Phage Display and Affinity Selection Using Recombinant Protein Baits

Published on: February 16, 2014

Using Phage Display to Develop Ubiquitin Variant Modulators for E3 Ligases

Using Phage Display to Develop Ubiquitin Variant Modulators for E3 Ligases

Published on: August 27, 2021

Related Experiment Videos

Last Updated: Jun 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

A Protocol for Phage Display and Affinity Selection Using Recombinant Protein Baits

A Protocol for Phage Display and Affinity Selection Using Recombinant Protein Baits

Published on: February 16, 2014

Using Phage Display to Develop Ubiquitin Variant Modulators for E3 Ligases

Using Phage Display to Develop Ubiquitin Variant Modulators for E3 Ligases

Published on: August 27, 2021

Area of Science:

Medicinal Chemistry
Drug Discovery
Biotechnology

Background:

Peptide macrocycles offer metabolic stability and selective binding for therapeutic applications.
Covalent macrocycles show promise but are underexplored for disrupting protein-protein interactions (PPIs).
Phage and mRNA display methods have advanced macrocycle discovery.

Purpose of the Study:

To develop a directed counter-selection method for identifying covalent macrocyclic ligands targeting PPIs.
To demonstrate the method's utility using the SARS-CoV-2 spike-ACE2 interaction.
To identify novel covalent inhibitors of this critical viral PPI.

Main Methods:

Utilized a phage display screening platform with a chemically modified library.
Employed binary and ternary screenings with an aryl fluorosulfate electrophile.
Applied a directed counter-selection strategy to isolate specific binders.

Main Results:

Successfully identified covalent macrocyclic inhibitors of the SARS-CoV-2 spike-ACE2 interaction.
Demonstrated irreversible antiviral activity against live SARS-CoV-2 virus.
Validated the efficacy of the directed counter-selection method for covalent macrocycle discovery.

Conclusions:

The developed screening platform is effective for discovering covalent macrocyclic drugs targeting PPIs.
This method enables the identification of inhibitors with irreversible binding and long-lasting effects.
The approach holds significant potential for developing novel therapeutics for various diseases.