Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Gene Regulation During Sporulation01:17

Gene Regulation During Sporulation

Sporulation is a complex developmental process that allows certain Gram-positive bacteria, such as Bacillus subtilis and Clostridium species, to survive extreme environmental conditions. This process is tightly regulated by a series of signaling cascades and transcriptional controls, ensuring the formation of a highly resistant endospore.Sporulation is triggered by unfavorable conditions, such as nutrient depletion, and is governed by a phosphorelay system. One of the sensor kinases, such as...

You might also read

Related Articles

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

Sort by
Same author

AURORA A interacts with DICER and SETD2 to promote S-phase progression.

EMBO reports·2026
Same author

Structure-Based Design, Synthesis, and Evaluation of Novel Ponatinib Derivatives With a Significantly Altered Selectivity Profile.

ChemMedChem·2026
Same author

On the Scope of DCAF1-Recruiting PROTACs Degrading Protein Kinases.

Journal of medicinal chemistry·2026
Same author

p21-Activated Kinase (PAK) Group I-Targeting Inhibitors Promote the Dimeric Conformation in Live Cells.

ACS chemical biology·2026
Same author

The structural basis for LRRK2's activation and autoinhibition.

bioRxiv : the preprint server for biology·2026
Same author

The "one-and-a-half" minimally invasive transforaminal lumbar interbody fusion: a single-center retrospective case series.

Journal of neurosurgery. Spine·2026
Same journal

Lipid Metabolic Labeling to Study Site- and Lipid-Specific Long-Chain <i>S</i>-Acylation Dynamics.

ACS chemical biology·2026
Same journal

Inositol Thiophosphates as Inhibitors of Mammalian, Plant, and Fungal Phytases.

ACS chemical biology·2026
Same journal

Synthesis and Characterization of the Spectroscopic and Imaging Utilities of Two Indole-Based Cyan Fluorescent Nucleoside Analogues.

ACS chemical biology·2026
Same journal

Indole Ring Expansion and Rearrangement-Enabled Quinoline Scaffold Formation in the Biosynthesis of the Antitumor Monoterpene Indole Alkaloid Camptothecin.

ACS chemical biology·2026
Same journal

Intracellular Delivery of Peptides and Proteins with an Engineered Membrane Translocation Domain.

ACS chemical biology·2026
Same journal

Development of Next-Generation Fluoroacetamidine-Containing Activity-Based Probes for the Selective Labeling of the Protein Arginine Deiminases (PADs).

ACS chemical biology·2026
See all related articles

Related Experiment Video

Updated: Jun 15, 2026

Semi-automated Biopanning of Bacterial Display Libraries for Peptide Affinity Reagent Discovery and Analysis of Resulting Isolates
13:49

Semi-automated Biopanning of Bacterial Display Libraries for Peptide Affinity Reagent Discovery and Analysis of Resulting Isolates

Published on: December 6, 2017

12.0K

Overcoming Ligand Discovery Challenges: Developing Peptide-Based Tracers for SPSB2.

Christopher Lenz1,2, Lewis Elson1,2, Johannes Dopfer1,2

  • 1Institute for Pharmaceutical Chemistry, Johann Wolfgang Goethe-University, Max-von-Laue-Straße 9, Frankfurt am Main 60438, Germany.

ACS Chemical Biology
|December 8, 2025
PubMed
Summary
This summary is machine-generated.

Developing cell-penetrating peptides (CPPs) enhances the delivery of polar degron-based molecules for E3 ligase ligand design. This strategy enables potent target engagement (TE) crucial for PROteolysis TArgeting Chimeras (PROTACs) development.

More Related Videos

Constructing Thioether/Vinyl Sulfide-tethered Helical Peptides Via Photo-induced Thiol-ene/yne Hydrothiolation
11:09

Constructing Thioether/Vinyl Sulfide-tethered Helical Peptides Via Photo-induced Thiol-ene/yne Hydrothiolation

Published on: August 1, 2018

11.1K
Development of a 68Gallium-Labeled D-Peptide PET Tracer for Imaging Programmed Death-Ligand 1 Expression
09:06

Development of a 68Gallium-Labeled D-Peptide PET Tracer for Imaging Programmed Death-Ligand 1 Expression

Published on: February 3, 2023

1.9K

Related Experiment Videos

Last Updated: Jun 15, 2026

Semi-automated Biopanning of Bacterial Display Libraries for Peptide Affinity Reagent Discovery and Analysis of Resulting Isolates
13:49

Semi-automated Biopanning of Bacterial Display Libraries for Peptide Affinity Reagent Discovery and Analysis of Resulting Isolates

Published on: December 6, 2017

12.0K
Constructing Thioether/Vinyl Sulfide-tethered Helical Peptides Via Photo-induced Thiol-ene/yne Hydrothiolation
11:09

Constructing Thioether/Vinyl Sulfide-tethered Helical Peptides Via Photo-induced Thiol-ene/yne Hydrothiolation

Published on: August 1, 2018

11.1K
Development of a 68Gallium-Labeled D-Peptide PET Tracer for Imaging Programmed Death-Ligand 1 Expression
09:06

Development of a 68Gallium-Labeled D-Peptide PET Tracer for Imaging Programmed Death-Ligand 1 Expression

Published on: February 3, 2023

1.9K

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Drug Discovery

Background:

  • Developing novel E3 ligase ligands is critical for heterobivalent molecules like PROteolysis TArgeting Chimeras (PROTACs).
  • Assessing target engagement (TE) and characterizing protein-protein interactions (PPIs) are essential for drug discovery.
  • Polar degrons, recognized by E3 ligases, are promising starting points for E3 ligand design but face cellular delivery challenges.

Purpose of the Study:

  • To develop effective in vitro and in cellulo target engagement (TE) strategies for polar degron-based peptides.
  • To investigate the use of polycationic cell-penetrating peptides (CPPs) for enhancing the cellular delivery of degron sequences.
  • To establish a model system using the SPRY domain-containing SOCS box protein 2 (SPSB2) E3 ligase.

Main Methods:

  • Conjugation of various polycationic cell-penetrating peptides (CPPs) to degron sequences.
  • High-resolution crystal structure determination.
  • Biophysical techniques (e.g., SPR, ITC) for assessing ligand binding and modifications.
  • Confocal microscopy and Bioluminescence Resonance Energy Transfer (BRET)-based assays for cellular delivery and TE confirmation.

Main Results:

  • Demonstrated successful cellular delivery of degron-based peptides conjugated with CPPs.
  • Confirmed potent target engagement (TE) in cellulo.
  • Obtained high-resolution structural insights into the E3 ligase-ligand interactions.
  • Quantified the influence of CPP conjugation on binding affinity and cellular uptake using biophysical methods.

Conclusions:

  • Polycationic CPPs can effectively facilitate the cellular delivery of polar degron-based peptides.
  • This approach enables potent target engagement (TE), advancing the design of E3 ligase ligands for PROTACs.
  • The study provides a robust platform for developing and evaluating novel E3 ligase ligands and PROTACs.