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

Targeted Cancer Therapies

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...

Covalently Linked Protein Regulators

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....

Covalently Linked Protein Regulators

Covalently Linked Protein Regulators

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...

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...

Drug-Receptor Bonds

Drug-Receptor Bonds

Drug-receptor bonds are formed through various chemical forces when drugs interact with target cells. Covalent bonds, strong and irreversible, are exemplified by DNA-alkylating anticancer agents that inhibit cell division. However, such irreversible drug binding lacks selectivity and can modify the DNA of the surrounding healthy cells. Covalent binding often contributes to tissue toxicity, as seen with chloroform and paracetamol metabolites binding to the liver, causing hepatotoxicity.
In...

You might also read

Related Articles

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

Sort by

Same author

Protein Post-Translational Modification-Inspired Regulation of Peptide Coacervation in Living Cells for Pro-Necroptotic Kinase Delivery.

Journal of the American Chemical Society·2026

Same author

AI-Driven De Novo Binder Design: From Structure Prediction to Closed-Loop Optimization.

Computational and structural biotechnology journal·2026

Same author

Antibody-Drug Conjugates Targeting Resistance-Associated Signaling Pathways: Recent Advances and Future Perspectives.

International journal of molecular sciences·2026

Same author

Clinically relevant stereochemistry reprograms amyloid proteome for aggregation cross-talk-conferred neuroprotection.

Science advances·2026

Same author

Sulfatase-responsive phase-separating peptide coacervates target stress granules to reverse sorafenib resistance in hepatocellular carcinoma.

Acta biomaterialia·2026

Same author

Oligomerization Propensity Governs Self-Assembly Morphology: Insights from Steady-State Oligomer Analysis.

Analytical chemistry·2025

Same journal

Ti/Sr Gradient Doping with SrTiO<sub>3</sub> Coating for Mitigating Strain and Oxygen Loss in Ni-Rich Cathode.

ACS applied materials & interfaces·2026

Same journal

Metallic Lead to Perfect Perovskite: A Bottom-Up Vapor-Assisted Colloidal Strategy for High-Performance Solar Cells.

ACS applied materials & interfaces·2026

Same journal

Two-Dimensional VSe<sub>2</sub>@Polypyrrole Heterostructure Enables Stable High-Rate Lithium-Sulfur Batteries.

ACS applied materials & interfaces·2026

Same journal

A Multifunctional Hydrogel Integrating Hemostatic, Antioxidant, and Antibacterial Properties for Infected and Diabetic Wound Regeneration.

ACS applied materials & interfaces·2026

Same journal

Tunable Interfacial to Filamentary Resistive Switching Mechanism in Room-Temperature-Grown Amorphous YBa<sub>2</sub>Cu<sub>3</sub>O<sub><i>x</i></sub> with Excess Cu Addition.

ACS applied materials & interfaces·2026

Same journal

Bioinspired Rhombic VO<sub>2</sub> Metasurface with Low Solar Absorptance for Self-adaptive All-Weather Building Thermal Management.

ACS applied materials & interfaces·2026

See all related articles

Search research articles

Related Experiment Video

Updated: Jan 14, 2026

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

Peptide-Based Targeted Covalent Inhibitors.

Fangyu Cao¹, Ruo-Chen Guo¹, Zeyu Zhang¹

¹Key Laboratory of Functional Polymer Materials, Ministry of Education, State Key Laboratory of Medicinal Chemical Biology, Institute of Polymer Chemistry, College of Chemistry, Nankai University, 94 Weijin Road, Tianjin 300071, China.

ACS Applied Materials & Interfaces

|October 27, 2025

Summary

This summary is machine-generated.

Peptide-based covalent inhibitors offer targeted drug delivery and improved selectivity. Advanced delivery systems utilizing peptide self-assembly enhance their clinical potential by overcoming limitations like poor membrane permeability.

Keywords:

covalent drugs disease therapy drug delivery peptides stimuli-responsiveness

More Related Videos

Peptide-based Identification of Functional Motifs and their Binding Partners

Peptide-based Identification of Functional Motifs and their Binding Partners

Published on: June 30, 2013

Covalent Fragment Screening Using the Quantitative Irreversible Tethering Assay

Covalent Fragment Screening Using the Quantitative Irreversible Tethering Assay

Published on: February 28, 2025

Related Experiment Videos

Last Updated: Jan 14, 2026

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

Peptide-based Identification of Functional Motifs and their Binding Partners

Peptide-based Identification of Functional Motifs and their Binding Partners

Published on: June 30, 2013

Covalent Fragment Screening Using the Quantitative Irreversible Tethering Assay

Covalent Fragment Screening Using the Quantitative Irreversible Tethering Assay

Published on: February 28, 2025

Area of Science:

Medicinal Chemistry
Drug Delivery
Nanotechnology

Background:

Covalent inhibitors are advanced therapeutics with improved selectivity and efficacy in overcoming drug resistance.
Peptide moieties are increasingly used as ligands in covalent inhibitors due to their binding affinity and biocompatibility.
Challenges in clinical translation include poor membrane permeability and in vivo stability of peptide-based covalent inhibitors.

Purpose of the Study:

To review recent advancements in covalent inhibitors featuring peptide ligands or delivered via peptide assemblies.
To explore the design strategies, mechanisms, and applications of peptide-based covalent inhibitors.
To discuss the role of supramolecular assemblies in enhancing covalent inhibitor delivery and efficacy.

Main Methods:

Systematic review of literature on peptide-based covalent inhibitors and their delivery systems.
Analysis of structure-activity relationships and design strategies for targeted covalent inhibition.
Evaluation of self-assembled peptide nanostructures as platforms for drug delivery.

Main Results:

Peptide ligands enhance targeting and selectivity of covalent inhibitors.
Self-assembled peptide nanostructures show promise for controlled release and improved in vivo stability.
Controllable electrophilic warheads are crucial for mitigating off-target effects.

Conclusions:

Peptide-based covalent inhibitors and their delivery systems represent a promising frontier in drug development.
Overcoming current limitations through advanced delivery strategies is key for clinical translation.
Future research should focus on optimizing stability, permeability, and targeted release for next-generation covalent drugs.